CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface

Lead Research Organisation: University of Bristol
Department Name: Chemistry

Abstract

"Everything that living things do can be understood in terms of the jigglings and wigglings of atoms" as Richard Feynman provocatively stated nearly fifty years ago. But how can we 'see' this wiggling and jiggling and understand how it drives biology? Increasingly, computer simulations of biological macromolecules are helping to meet this challenge. Experiments can provide detailed structures of biological macromolecules such as proteins, but it is hard to study directly how the structures of individual molecules change on short timescales as they function. Similarly it is not yet possible to study directly by experiment alone the molecular mechanisms of fast processes such as chemical reactions in enzymes or ion transport through membranes. Simulations based on fundamental physics offer the potential of filling-in these crucial 'gaps', modelling how proteins and other biomolecules move, fluctuate, interact, react and function.
Physics-based simulations complement experiments in building a molecular level understanding of biology: they can test hypotheses and interpret and analyse experimental data in terms of interactions at the atomic level. A wide variety of simulation techniques have been developed, applicable to a range of different problems in biomolecular science. Simulations have already shown their worth in helping to analyse how enzymes catalyse biochemical reactions, and how proteins adopt their functional structures. They can help in the design of drugs and catalysts, and in understanding the molecular basis of disease. And simulations have played a key role in developing the conceptual framework now at the heart of biomolecular science, that is, the understanding that the way that biological molecules move and flex - their dynamics - is central to their function, demonstrating the truth of Feynman's assertion.
Developing methods from chemical physics and computational science will open exciting new opportunities in biomolecular science, including in drug design and development, synthetic biology, biotechnology and biocatalysis. Much biomolecular simulation demands HEC resources: e.g. large-scale simulations of biological machines such as the ribosome, proton pumps and motors, membrane receptor complexes and even whole viruses. A particular challenge is the integration of simulations across length and timescales: different types of simulation method are required for different types of problems). We work to develop 'multiscale' modelling and simulation methods to tackle these large problems, in areas such as drug metabolism and transport.

Planned Impact

Biomolecular simulation and modelling is vital e.g. to the pharmaceutical industry, where it is an integral part of drug design and development (e.g. in structure-based drug design and predictions of drug metabolism). Pharma needs well-trained scientists in this area, and new methods (e.g. for prediction of drug binding affinities). CCP-BioSim contributes directly to both of these key requirements. Our activities also promote collaboration between simulation and experiment; biomolecular simulation is central to multidisciplinary research programmes. CCP-BioSim, and the computational tools it develops and contributes to, increase biological applications of high-end computing (HEC). As well as biosimulation specialists, a broad community of industrial and academic bioscientists investigating biomolecular structure and function will benefit from CCP-BioSim. Longer term, CCP-BioSim has the potential to contribute to improvements in health and quality of life. The bioscience community will benefit through access to tools, training, and trained simulation specialists that enable novel and more effective multidisciplinary projects where computational methods enhance and extend their core experimental approaches. CCP-BioSim helps to train scientists able to work across the theory/experimental boundary. Impacts on health will come from the application of the methods fostered and disseminated by CCP-BioSim to drug design and discovery. CCP-BioSim will a) help to train new researchers b) develop and disseminate advanced computational methods and c) provide a forum to enhance industrial-academic research links (members of the management group have strong links with many pharmaceutical/biotech companies, e.g. AstraZeneca, Vernalis, Phaminox, GSK, Evotec, Pfizer, Sanofi, Astex, etc.). There is also broader impact of biomolecular simulation in areas such as drug delivery and synthetic biology. Finally, vast amounts of data are coming from genomics, proteomics, glycomics and structural biology. Developments in X-ray crystallography, high-throughput sequencing, protein production and crystallization, EM, SAXS, NMR and mass spectrometry, combined with modern data storage capacities have vastly increased the quantity of information available in structural biology, proteomics and genomics databases. Investment in understanding and interpretation in terms of biological function is vital to make use of this information. Biomolecular simulation is essential to enhance understanding and guide further experiments, especially as the quantity and complexity of biological data is immense and continues to grow. Improved understanding of biomolecular interactions and their consequences is not just of fundamental interest, but also benefits applied science. Progress in understanding biomacromolecules requires an integrated approach using a range of biophysical techniques, both experimental and computational. Biomolecular simulation will help to use these data to develop new drugs, catalysts and nanotechnology.

Publications

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Carvalheda C (2016) Water dynamics and proton translocation in cytochrome cbb3 oxidase in Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Carvalheda CA (2017) Insights into proton translocation in cbb3 oxidase from MD simulations. in Biochimica et biophysica acta. Bioenergetics

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Catlow CR (2020) Science to enable the circular economy. in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

 
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Title An expandable, modular de novo protein platform for precision redox engineering 
Description Pioneering study signals new era of environment-friendly programmable bioelectronics Image shows the design of a protein nanowire, with the green arrow indicating electron flow. Ross Anderson Image shows structural analysis of the protein-based wire, comparing the model of the designed protein (shown in red) with the experimentally determined structure (in grey). Ross Anderson Press release issued: 25 July 2023 Researchers have created a unique microscopic toolkit of 'green' tuneable electrical components, paving the way for a new generation of bioelectronic devices and sensors. The University of Bristol-led study, published today in The Proceedings of the National Academy of Sciences (PNAS), demonstrates how to make conductive, biodegradable wires from designed proteins. These could be compatible with conventional electronic components made from copper or iron, as well as the biological machinery responsible for generating energy in all living organisms. The miniscule wires are the size of transistors on silicon chips or one thousandth of the breadth of the finest human hair. They are made completely of natural amino acids and heme molecules, found in proteins such as hemoglobin, which transports oxygen in red blood cells. Harmless bacteria were used for their manufacture, eliminating the need for potentially complex and environmentally damaging procedures commonly used in the production of synthetic molecules. Lead author Ross Anderson, Professor of Biological Chemistry at the University of Bristol, said: "While our designs take inspiration from the protein-based electronic circuits necessary for all life on Earth, they are free from much of the complexity and instability that can prevent the exploitation of their natural equivalents on our own terms. We can also build these minute electronic components to order, specifying their properties in a way that is not possible with natural proteins." Leading experts in biomolecular engineering and simulation worked together to produce this unique new method of designing tailor-made proteins with tuneable electronic properties. The multidisciplinary team used advanced computational tools to design simple building blocks that could be combined into longer, wire-like protein chains for conducting electrons. They were able to visualise the structures of these wires using protein X-ray crystallography and electron cryo-microscopy (cryo-EM), techniques which allow structures to be viewed in the finest detail. Pushing the technical boundaries of cryo-EM, images of the smallest individual protein ever studied were obtained with this technique. Ultimately, these nanoscale designer wires have the potential to be used in a wide range of applications, including biosensors for the diagnosis of diseases and detection of environmental pollutants. It is also hoped this invention will form the foundation of new electrical circuits for creating tailor-made catalysts for green industrial biotechnology and artificial photosynthetic proteins for capturing solar energy. The breakthrough was possible thanks to a £4.9 million grant from the Biotechnology and Biological Science Research Council (BBSRC), the UK's largest bioscience funder, which resulted in a five-year project entitled 'The Circuits of Life' involving the Universities of Bristol, Portsmouth, East Anglia, and University College London (UCL). The team harnessed their expertise in protein design, electron transfer, biomolecular simulation, structural biology and spectroscopy, gaining insight into how electrons flow through natural biological molecules, a fundamental process which underpins cellular respiration and photosynthesis. Further advances are expected as the project, which began last year, progresses, presenting significant opportunities to help meet the transition to net zero and more sustainable industrial processes. Co-author Adrian Mulholland, Professor of Chemistry at the University of Bristol, said: "These proteins show how protein design is increasingly delivering practically useful tools. They offer exciting possibilities as components for engineering biology and also are great systems for investigating the fundamental mechanisms of biological electron transfer." Paper 'An expandable, modular de novo protein platform for precision redox engineering' by George H. Hutchins, Claire E.M. Noble, Adrian Bunzel et al published in PNAS 
Type Of Material Technology assay or reagent 
Year Produced 2023 
Provided To Others? Yes  
Impact Pioneering study signals new era of environment-friendly programmable bioelectronics Image shows the design of a protein nanowire, with the green arrow indicating electron flow. Ross Anderson Image shows structural analysis of the protein-based wire, comparing the model of the designed protein (shown in red) with the experimentally determined structure (in grey). Ross Anderson Press release issued: 25 July 2023 Researchers have created a unique microscopic toolkit of 'green' tuneable electrical components, paving the way for a new generation of bioelectronic devices and sensors. The University of Bristol-led study, published today in The Proceedings of the National Academy of Sciences (PNAS), demonstrates how to make conductive, biodegradable wires from designed proteins. These could be compatible with conventional electronic components made from copper or iron, as well as the biological machinery responsible for generating energy in all living organisms. The miniscule wires are the size of transistors on silicon chips or one thousandth of the breadth of the finest human hair. They are made completely of natural amino acids and heme molecules, found in proteins such as hemoglobin, which transports oxygen in red blood cells. Harmless bacteria were used for their manufacture, eliminating the need for potentially complex and environmentally damaging procedures commonly used in the production of synthetic molecules. Lead author Ross Anderson, Professor of Biological Chemistry at the University of Bristol, said: "While our designs take inspiration from the protein-based electronic circuits necessary for all life on Earth, they are free from much of the complexity and instability that can prevent the exploitation of their natural equivalents on our own terms. We can also build these minute electronic components to order, specifying their properties in a way that is not possible with natural proteins." Leading experts in biomolecular engineering and simulation worked together to produce this unique new method of designing tailor-made proteins with tuneable electronic properties. The multidisciplinary team used advanced computational tools to design simple building blocks that could be combined into longer, wire-like protein chains for conducting electrons. They were able to visualise the structures of these wires using protein X-ray crystallography and electron cryo-microscopy (cryo-EM), techniques which allow structures to be viewed in the finest detail. Pushing the technical boundaries of cryo-EM, images of the smallest individual protein ever studied were obtained with this technique. Ultimately, these nanoscale designer wires have the potential to be used in a wide range of applications, including biosensors for the diagnosis of diseases and detection of environmental pollutants. It is also hoped this invention will form the foundation of new electrical circuits for creating tailor-made catalysts for green industrial biotechnology and artificial photosynthetic proteins for capturing solar energy. The breakthrough was possible thanks to a £4.9 million grant from the Biotechnology and Biological Science Research Council (BBSRC), the UK's largest bioscience funder, which resulted in a five-year project entitled 'The Circuits of Life' involving the Universities of Bristol, Portsmouth, East Anglia, and University College London (UCL). The team harnessed their expertise in protein design, electron transfer, biomolecular simulation, structural biology and spectroscopy, gaining insight into how electrons flow through natural biological molecules, a fundamental process which underpins cellular respiration and photosynthesis. Further advances are expected as the project, which began last year, progresses, presenting significant opportunities to help meet the transition to net zero and more sustainable industrial processes. Co-author Adrian Mulholland, Professor of Chemistry at the University of Bristol, said: "These proteins show how protein design is increasingly delivering practically useful tools. They offer exciting possibilities as components for engineering biology and also are great systems for investigating the fundamental mechanisms of biological electron transfer." Paper 'An expandable, modular de novo protein platform for precision redox engineering' by George H. Hutchins, Claire E.M. Noble, Adrian Bunzel et al published in PNAS 
URL https://www.bristol.ac.uk/news/2023/july/protein-nanowires.html
 
Title Annual report to EPSRC; details below 
Description HECBioSim, the UK HEC Biomolecular Simulation Consortium, was established in March 2013, and works closely with and complements CCP-BioSim (the UK Collaborative Computational Project for Biomolecular Simulation at the Life Sciences Interface). Most of the members of the Consortium are experienced users of high end computing. Biomolecular simulations are now making significant contributions to a wide variety of problems in drug design and development, biocatalysis, bio and nano-technology, chemical biology and medicine. The UK has a strong and growing community in this field, recognized by the establishment in 2011 by the EPSRC of CCP-BioSim (ccpbiosim.ac.uk), and its renewal in 2015. There is a clear, growing and demonstrable need for HEC in this field. Members of the Consortium have, for example, served on the HECToR and ARCHER Resource Allocation Panel. The Consortium welcomes members across the whole biomolecular sciences community, and we are currently (and will remain) open to new members (unlike some consortia). Since establishing the Consortium, several new members (FLG, DH, ER) have joined the Management Group. Many of the projects awarded ARCHER time under the Consortium do not involve CCP-BioSim or HECBioSim Management Group members, demonstrating the openness of HECBioSim and its support of the biomolecular simulation community in the UK. A number of other researchers have joined and it is our expectation that other researchers will join HECBioSim in the future. We actively engage with structural and chemical biologists and industrial researchers. We foster interactions between computational, experimental and industrial scientists (see the example case studies; members of the Consortium have excellent links with many pharmaceutical, chemical and biotechnology companies). Details of HECBioSim are available via our webpages at: http://www.hecbiosim.ac.uk Applications are made through the website http://www.hecbiosim.ac.uk and reviewed at one of the series of regular panel meetings. A list of successful HECtime allocations on ARCHER is available at:http://www.hecbiosim.ac.uk/applications/successfulprojects All proposals are of course subject to scientific and technical review, but we have the philosophy of supporting the best science to deliver the highest impact, rather than focusing on supporting development of a couple of codes. An allocation panel (with changing membership) meets twice yearly to judge proposals and requests for AUs; projects are assessed competitively: any groups in the UK can apply. All submitted proposals receive constructive feedback from the allocation panel. The HECBioSim website also provides forums for the biomolecular simulation community, a wiki hosting useful how-tos and user guides, and software downloads (currently FESetup and Longbow). Our lead software development project between Nottingham (Charlie Laughton and Gareth Shannon) and Daresbury (James Gebbie), we have developed a remote job submission tool, 'Longbow' (see below). The tool is designed to reproduce the look and feel of local MD packages, but to stage data and submit jobs to a large HPC resource, such as ARCHER, in a manner invisible to the user. Workshops and New Opportunities No more than half a page detailing upcoming workshops and meetings. Also include discussion of other areas which are potentially of interest to other HEC Consortia and opportunities for cross CCP /HEC working. Workshops are listed below and can be found on the HECBioSim Website We work closely with CCP-BioSim, for example in organizing training workshops and meetings. Our activities are outlined at www.hecbiosim.ac.uk Examples of forthcoming meetings include: Computational Molecular Science 2017 - on Sunday 19 March 2017 17th European Seminar on Computational Methods in Quantum Chemistry - on Tuesday 11 July 2017 Frontiers of Biomolecular Simulation Southampton, September 2016 Issues and Problems Short discussion of any issues or problems that the HEC Consortium faces including issues with the ARCHER service, funding, management of allocation and staffing. This is also a good opportunity to highlight to the SLA committee any issues that the Consortium may have experienced with their SLA support during the reporting period. Details of SLA activities are given in the SLA report. Dr. James Gebbie provides support to HECBioSIm through the SLA. He has been very helpful in the construction of the HECBioSim webpages (hecbiosim.ac.uk). James also worked with Dr. Gareth Shannon on the development of Longbow (See above). In the past year, members of the Consortium faced some queuing problems; close to the end of the first allocation period in particular, there were long queuing times, which led to problems in completing jobs and using allocated time. Throughput has been a real problem in the past few months. Membership Please provide a full list of existing members and their institutions, highlighting any new members that have joined the consortium during the reporting period. If available please provide information on the number of distinct users that have accessed ARCHER via the Consortium during this reporting period. Below is a list of PIs with HECBioSim projects in the current reporting period: Agnes Noy, University of York - new to this reporting period Alessandro Pandini, Brunel University London Arianna Fornili, Queen Mary University of London Cait MacPhee, University of Edinbrurgh - new to this reporting period Charlie Laughton, University of Nottingham Clare-Louise Towse, University of Bradford - new to this reporting period D Flemming Hansen, University College London - new to this reporting period David Huggins, Aston University Edina Rosta, King's College London Francesco Gervasio, University College London Ian Collinson, University of Bristol - new to this reporting period Irina Tikhonova, Queen's University Belfast Jiayun Pang, University of Greenwich Jonathan Doye, University of Oxford Julien Michel, University of Edinburgh Mario Orsi, UWE Bristol Michele Vendruscolo, University of Cambridge Michelle Sahai, University of Roehampton Philip Biggin, University of Oxford Richard Sessions, University of Bristol Stephen Euston, Heriot-Watt University Syma Khalid, University of Southampton PIs in HECBioSIm outside of current allocation period Peter Bond, University of Cambridge Richard Bryce, University of Manchester Juan Antonio Bueren-Calabuig, University of Edinburgh Christo Christov, Northumbria University Anna K Croft, University of Nottingham Jonathan Essex, University of Southampton Robert Glen, University of Cambridge Sarah A Harris, University of Leeds Jonathan Hirst, University of Nottingham Douglas Houston, University of Edinburgh Dmitry Nerukh, Aston University Andrei Pisliakov, University of Dundee Mark Sansom, University of Oxford Marieke Schor, University of Edinburgh Gareth Shannon, University of Nottingham Tatyana Karabencheva-Christova, Northumbria University There are currently 164 members of HECBioSim (i.e. users of HECBioSIm ARCHER time), included the above PIs. 20 new users have been added since January 2016. World class and world leading scientific output: ARCHER should enable high quality and world-leading science to be delivered. This should generate high impact outputs and outcomes that increase the UK's position in world science. • If all the publications relating to the work of the Consortium for this reporting period have been added to ResearchFish / will be added to ResearchFish by the end of the ResearchFish reporting exercise, please indicate this below. • If submission of a full list of publications to the Consortium record/s in ResearchFish has not been possible for this reporting period please provide a list of publications that have resulted from work performed on ARCHER by the Consortium during this reporting period (this can be included as a separate attachment). • For the reporting period please provide a bullet pointed list of key / important research findings that has resulted from work performed on ARCHER by the Consortium. Please reference any related publications. • For the reporting period please include a bullet pointed list of any relevant press announcements and other communications of significance to an international community. All publications can be found in ResearchFish, and have been added by individual researchers. A selection of illustrative highlights are provided below: Julien Michel (University of Edinburgh) New molecular simulation methods have enabled for the first time a complete description of the interactions of several drug-like small molecules with an intrinsically disordered region of the oncoprotein MDM2, as well as the effect of post-translational modifications on the dynamics of this protein. The results obtained suggest new medicinal chemistry strategies to achieve potent and selective inhibition of MDM2 for cancer therapies. Publication: Elucidation of Ligand-Dependent Modulation of Disorder-Order Transitions in the Oncoprotein MDM2 http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004282 Impact of Ser17 Phosphorylation on the Conformational Dynamics of the Oncoprotein MDM2 http://pubs.acs.org/doi/abs/10.1021/acs.biochem.6b00127 An outreach document is being prepared by EPCC to showcase a lab project on isoform selective inhibition that has benefited from both HECBioSim and EPCC ARCHER allocations. Syma Khalid (Chemistry, Southampton) Publication: OmpA: A Flexible Clamp for Bacterial Cell Wall Attachment Samsudin F, Ortiz-Suarez ML, Piggot TJ, Bond PJ, Khalid S (2016). "OmpA: a Flexible Clamp for Bacterial Cell Wall Attachment", Structure, 24(12):2227-2235 With Singapore National Center for Biotechnology. Sarah Harris (Physics, Leeds) In collaboration with the experimental biochemistry group lead by Radford at Leeds, Sarah Harris used ARCHER time to show how chaperones help outer membrane proteins to fold, see: Schiffrin B, Calabrese AN, Devine PWA, Harris SA, Ashcroft AE, Brockwell DJ, Radford SE "Skp is a multivalent chaperone of outer-membrane proteins" Nature Structural and Molecular Biology 23 786-793, 2016. DOI:10.1038/nsmb.3266 Michelle Sahai (Department of Life Sciences, Roehampton) Publication: Combined in vitro and in silico approaches to the assessment of stimulant properties of novel psychoactive substances - The case of the benzofuran 5-MAPB. Progress in Neuro-Psychopharmacology and Biological Psychiatry 75, Pages 1-9 (2017) https://www.ncbi.nlm.nih.gov/pubmed/27890676 Phil Biggin (Biochemistry, Oxford) Outputs that have used HECBioSim time: 1. Steered Molecular Dynamics Simulations Predict Conformational Stability of Glutamate Receptors. Musgaard M, Biggin PC. J Chem Inf Model. 2016 Sep 26;56(9):1787-97. doi: 10.1021/acs.jcim.6b00297. 2. Kainate receptor pore-forming and auxiliary subunits regulate channel block by a novel mechanism. Brown PM, Aurousseau MR, Musgaard M, Biggin PC, Bowie D. J Physiol. 2016 Apr 1;594(7):1821-40. doi: 10.1113/JP271690. 3. Role of an Absolutely Conserved Tryptophan Pair in the Extracellular Domain of Cys-Loop Receptors. Braun N, Lynagh T, Yu R, Biggin PC, Pless SA. ACS Chem Neurosci. 2016 Mar 16;7(3):339-48. doi: 10.1021/acschemneuro.5b00298. 4. Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes. Dawe GB, Musgaard M, Aurousseau MR, Nayeem N, Green T, Biggin PC, Bowie D. Neuron. 2016 Mar 16;89(6):1264-76. doi: 10.1016/j.neuron.2016.01.038. Covered by 7 news outlets: I. Health Canal (http://www.healthcanal.com/brain-nerves/70646-what-makes-the-brain-tick-so-fast.html) II. Health Medicine Network (http://healthmedicinet.com/i/scientists-reveal-how-the-brain-processes-information-with-lightning-speed/) III. News Medical (http://www.news-medical.net/news/20160227/Scientists-reveal-how-the-brain-processes-information-with-lightning-speed.aspx) IV. Wired (http://www.wired.co.uk/article/what-we-learned-about-the-brain-this-week-3) V. Alpha Galileo (http://www.alphagalileo.org/ViewItem.aspx?ItemId=161473&CultureCode=en) VI. Science Daily (https://www.sciencedaily.com/releases/2016/02/160225140254.htm) VII. Eureka Alert (https://www.eurekalert.org/pub_releases/2016-02/mu-wmt022516.php) Recommended by F1000 Prime: http://f1000.com/prime/726180600. 5. Accurate calculation of the absolute free energy of binding for drug molecules. Aldeghi M, Heifetz A, Bodkin MJ, Knapp S, Biggin PC. Chem Sci. 2016 Jan 14;7(1):207-218. Arianna Fornili (Biological and Chemical Sciences, Queen Mary University of London) Publication: Fornili, E. Rostkova, F. Fraternali, M. Pfuhl: Effect of RlC N-Terminal Tails on the Structure and Dynamics of Cardiac Myosin. Biophysical J. 110 (2016) 297A. More in preparation. Dmitry Nerukh (Engineering and Applied Science, Aston University) Important research findings: Distribution of ions inside a viral capsids influences the stability of the capsid Edina Rosta (Computational Chemistry, Kings College London) Highlighted publication: We have a joint experimental paper with the Vertessy group in JACS where we identified a novel arginine finger residue in dUTPase enzymes, and described the mechanism of action for this residue using crystallographic data, biochemical experiments, MD and QM/MM simulations thanks to HECBioSim. http://pubs.acs.org/doi/abs/10.1021/jacs.6b09012 Press release: Our joint paper with Jeremy Baumberg's group in Cambridge was published in Nature. http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_13-6-2016-16-52-4 Greater scientific productivity: As well as speed increases, the optimisation of codes for the ARCHER machine will enable problems to be solved in less time using fewer compute resources. • For the reporting period please provide a brief update on the progress of software development activities associated with the Consortium and the impact this has had on Consortium members and the broader research community. Our lead software development project between Nottingham (Charlie Laughton and Gareth Shannon) and Daresbury (James Gebbie), we have developed a remote job submission tool, 'Longbow' (see below). The tool is designed to reproduce the look and feel of local MD packages, but to stage data and submit jobs to a large HPC resource such as ARCHER in a manner invisible to the user. An open beta version was released unrestricted to the community in March 2015 (http://www.hecbiosim.ac.uk/longbow and via PyPI https://pypi.python.org ) with ~100 downloads. Functionality includes native support for biosimulation packages AMBER, CHARMM, GROMACS, LAMMPS and NAMD, native support for jobs on ARCHER, native support for jobs running on PBS and LSF schedulers, and support for three different job types (single, ensembles and multiple jobs). The software is written both as an application for users and an API for developers. CCP-EM have integrated Longbow into their developmental GUI, and shortly FESetup will ship with native support for job submission using Longbow. We are currently in talks with ClusterVision with respect to them distributing Longbow to their user base as a user friendly way for novices to interact with their systems. Longbow Longbow has been growing in popularity both amongst researchers within the biosimulation field and those in other fields. In this reporting period there have been five new releases of Longbow delivering a plethora of user requested features and bug fixes. Some of the key developments are summarised below: • Implemented a Recovery mode - Should the event happen that Longbow crashes or the system in which Longbow is controlling jobs from powers down. The user can now reconnect to the crashed session and carry on as if nothing happened. • Sub-Queuing - More and more system administrators are setting limits not just on the number of simulations that can run, but also on the number of jobs that can go into the queue. Longbow can now automatically detect this and implement its own queue feeding jobs into the system queue as slots open up. • Dis-connectible/Re-connectible Longbow sessions - A user can now launch Longbow to fire off all jobs and then disconnect, at a later date the user can re-establish the connection and download all results (no need for persistent connections anymore) • Ability to include scripts in the Longbow generated submit files. • Numerous stability, performance and bug fixes Longbow continues to be the submission engine that is used under the hood of the CCP-EM toolkit FLEX-EM. There are several other interesting projects that are making use of Longbow. A project by the energy efficient computing group (Hartree Center) are currently integrating Longbow with CK, a crowd sourced compilation optimisation tool aimed at finding efficient compilation configuration. A project by the Applications performance engineering group (Hartree Center) are currently integrating longbow into Melody, a runtime optimisation tool aimed at optimising runtime configuration of simulations. A project by the computational biology group (Hartree Center) an automated setup, launch and analysis platform for MD on protein-membrane simulations. Metrics Downloads (HECBioSim) 985 Downloads (PyPi) 3456 Increasing the UK's CSE skills base (including graduate and post doctorate training and support): This builds on the skills sets of trained people in HPC, both in terms of capacity and raising the overall skill level available to the sector. • For the reporting period please provide information on the number of PhDs and Post-Docs that have been trained in the use of ARCHER as a result of work relating to the Consortium. • For the reporting period please provide a bullet pointed list of training activities undertaken by the Consortium, providing information on the target audience and level of attendance. 125 PhD and PDRAs have been trained and have used ARCHER through HECBioSim. In the past 6 months alone that has included: PhD students: Marc Dämgen, University of Oxford Laura Domicevica, University of Oxford Matteo Aldeghi, University of Oxford Shaima Hashem, Queen Mary University of London Ruth Dingle, University College London Lucas Siemons, University College London Elvira Tarasova, Aston University Vladimiras Oleinikovas, University College London Havva Yalinca, University College London Daniel Moore, Queen's University Belfast Aaron Maguire, Queen's University Belfast Maxime Tortora, University of Oxford Michail Palaiokostas, UWE Bristol Wei Ding, UWE Bristol Ganesh Shahane, UWE Bristol Pin-Chia Hsu, University of Southampton Damien Jefferies, University of Southampton PDRA: Maria Musgaard, University of Oxford Teresa Paramo, University of Oxford Marieke Schor, University of Edinbrurgh Antonia Mey, University of Edinbrurgh Ioanna Styliari, University of Nottingham Ivan Korotkin, Aston University Silvia Gomez Coca, King's College London Giorgio Saladino, University College London Federico Comitani, University College London Robin Corey, University of Bristol Jordi Juarez-Jimenez, University of Edinburgh Predrag Kukic, University of Cambridge Giulia Tomba, University of Cambridge Deborah Shoemark, University of Bristol Georgios Dalkas, Heriot-Watt University Robin Westacott, Heriot-Watt University Firdaus Samsudin, University of Southampton Agnes Noy, University of Leeds (now EPSRC fellow at York). Please see below details of the training week held in June 2016 at the University of Bristol. 170 delegates attending the training which ran over 5 days. There is course content available on the HECBioSim Workshop Page CCPBioSim Training Week - Day 5: QM/MM enzyme reaction modelling - on Friday 10 June 2016 CCPBioSim Training Week - Day 4: Monte Carlo Methods for Biomodelling - on Thursday 09 June 2016 CCPBioSim Training Week - Day 3: Python for Biomodellers and FESetup - on Wednesday 08 June 2016 CCPBioSim Training Week - Day 2: Running and analysing MD simulations - on Tuesday 07 June 2016 CCPBioSim Training Week - Day 1: Enlighten: Tools for enzyme-ligand modelling - on Monday 06 June 2016 Past Workshops and Conferences: AMOEBA advanced potential energies workshop - on Friday 09 December 2016 Intel Training Workshop (Parallel programming and optimisation for Intel architecture) - on Wednesday 30 November 2016 3rd Workshop on High-Throughput Molecular Dynamics (HTMD) 2016 - on Thursday 10 November 2016 Free Energy Calculation and Molecular Kinetics Workshop - on Tuesday 13 September 2016 Going Large: tools to simplify running and analysing large-scale MD simulations on HPC resources - HECBioSim - on Wednesday 16 December 2015 This 1 day workshop dealt with Longbow, a Python tool created by HECBioSim consortium that allows use of molecular dynamics packages (AMBER, GROMACS, LAMMPS, NAMD) with ease from the comfort of the desktop, and pyPcazip, a flexible Python-based package for the analysis of large molecular dynamics trajectory data sets. Richard Henchman ( Chemistry, Manchester) I lectured on the CCP5 Summer School in 2015 in Manchester and 2016 in Lancaster for the Advanced Topic Biomolecular Simulation drawing on CCPBiosim training materials. Sarah Harris (Physics, Leeds) Agnes Noy Agnes Noy was trained to use ARCHER independently which helped her to obtain an Early-career EPSRC fellowship. The fellowship grant follows the study of supercoiling DNA by modelling (further funding) and introduces a new member to the community (grant is EPSRC (EP/N027639/1)). Increased impact and collaboration with industry: ARCHER does not operate in isolation and the 'impact' of ARCHER's science is converted to economic growth through the interfaces with business and industry. In order to capture the impacts, which may be economic, social, environmental, scientific or political, various metrics may be utilised. • For the reporting period please provide where possible information on Consortium projects that have been performed in collaboration with industry, this should include: o Details of the companies involved. o Information on the part ARCHER and the Consortium played. o A statement on the impact that the work has / is making. o If relevant, details of any in kind or cash contributions that have been associated with this work. • For the reporting period include a list of Consortium publications that have industrial co-authorship. • For the reporting period please provide details of the any other activities involving industrial participation e.g. activities involving any Industrial Advisory panels, attendance / participation in workshops and Consortium based activities. Examples of industrial engagement through HECBioSim include: Syma Khalid (Computational Biophysics, Southampton) Collaboration with Siewert-Jan Marrink (Netherlands) and Wonpil Im(USA) - paper is being written at the moment - also we have developed and tested the following computational tool as part of this project: http://www.charmm-gui.org/?doc=input/membrane We have signed an NDA with a company developing antibiotics (Auspherix) based on work published in Samsudin et al, Structure, 2016. The company provide us with experimental data and crucially the structures of their potential drug molecules, and we work out how they interact with the bacterial membrane. Press releases https://www.sciencedaily.com/releases/2016/11/161121094122.htm ARCHER time we got from HECBioSim was essential for this project. These are large simulations that are very computationally demanding. Julien Michel (Chemistry, Edinburgh) Industrial collaborations that have benefited from HECBioSim UCB was a project partner of EPSRC-funded research in the Michel lab on modelling binding of ligands to flexible proteins. HECBioSim supported the research via allocation of computing time on ARCHER. The work has been published. Impact of Ser17 phosphorylation on the conformational dynamics of the oncoprotein MDM2 Bueren-Calabuig, J. A. ; Michel, J. Biochemistry, 55 (17), 2500-2509, 2016 Elucidation of Ligand-Dependent Modulation of Disorder-Order Transitions in the Oncoprotein MDM2 Bueren-Calabuig, J. A. ; Michel, J. PLoS Comput. Biol. , 11(6): e1004282, 2015 International activities I represented HECBioSim at the MolSSI conceptualisation workshop in Houston (October 2016). Arianna Fornili (School of Biological and Chemical Sciences, Queen Mary University of London) This project is done in collaboration with experimental (NMR and SAXS) partners at King's College London (Dr. Mark Pfuhl and Dr. Elena Rostkova), with the final aim of providing a complete molecular model of how muscle contraction is regulated in the heart. Francesco Gervasio (Chemistry, UCL) A new collaboration with UCB on developing new approaches to sample cryptic binding sites of pharmaceutical interest was started. UCB co-sponsored a BBSRC-CASE PhD studentships. The code development and its application to interesting targets was made possible by the access to Archer. Phil Biggin (Biochemistry, Oxford) The following has industrial partners as co-authors: Accurate calculation of the absolute free energy of binding for drug molecules, Aldeghi M, Heifetz A, Bodkin MJ, Knapp S, Biggin PC. Chem. Sci., 2016,7, 207-218 doi: 10.1039/C5SC02678D. The GLAS scoring module for gromacs has yet to be implemented but that would also constitute industrial activity. Richard Henchman (Chemistry, Manchester) Industrial Collaboration I have one publication with an industrial co-author (Evotec), which Julien Michel is part of as well. Assessment of hydration thermodynamics at protein interfaces with grid cell theory, G. Gerogiokas, M. W. Y. Southey, M. P. Mazanetz, A. Heifetz, M. Bodkin, R. J. Law, R. H. Henchman and J. Michel, J. Phys. Chem. B, 2016, 120, 10442-10452. Strengthening of UK's international position: The impacts of ARCHER's science extend beyond national borders and most science is delivered through partnerships on a national or international level. • For the reporting period please provide a bullet pointed list of projects that have involved international collaboration. For each example please provide a brief summary of the part that ARCHER and the Consortium have played. • For the reporting period please provide a list of consortium publications with international co-authorship. • For the reporting period please detail any other international activities that the Consortium might be involved in (workshops, EU projects etc.). Examples of HECBioSim international engagement include: Michelle Sahai (Department of Life Sciences, Roehampton) Combined in vitro and in silico approaches to the assessment of stimulant properties of novel psychoactive substances - The case of the benzofuran 5-MAPB. Sahai MA, Davidson C, Khelashvili G, Barrese V, Dutta N, Weinstein H, Opacka-Juffry J. Prog Neuropsychopharmacol Biol Psychiatry. (2016) 75:1-9. doi: 10.1016/j.pnpbp.2016.11.004. co-authors affiliations include: Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University (WCMC), New York, NY, 10065, USA and HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute of Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, NY, 10065, USA. Author contribution: CD, MAS, HW and JOJ were responsible for the study concept and design. CD and VB collected and interpreted the voltammetry data. JOJ and ND conducted the ligand binding experiments and ND analysed the data. MAS (ARCHER user) and GK performed the molecular modelling studies and interpreted the findings. CD, MAS, GK and JOJ drafted the manuscript. All authors critically reviewed the content and approved the final version for publication. Dmitry Nerukh (Engineering and Applied Science, Aston University) Collaborations: • Prof. Makoto Taiji group (K-computer, MDGRAPE), Laboratory for Computational Molecular Design, Computational Biology Research Core, RIKEN Quantitative Biology Center (QBiC), Kobe, Japan • Prof. Reza Khayat group, City College of New York, United States • Prof. Artyom Yurov group, Immanuel Kant Baltic Federal University, Russian Federation • Prof. Nikolay Mchedlov-Petrosyan group, V.N. Karazin Kharkiv National University, Ukraine • Prof. Natalya Vaysfeld group, Odessa I.I.Mechnikov National University, Ukraine International activities: • International Workshop - Engineering bacteriophages for treating antimicrobial resistance using computational models. Dec. 2016, Aston University, UK Dmitry Nerukh group at Aston University collaborates with the group of Prof. Makoto Taiji (the deputy director of RIKEN Quantitative Biology Institute). Prof. Taiji group is the author and implementer of the fastest machine in the world for molecular dynamics simulations, MDGRAPE, as well as part of the team designing the K-computer and working on it (several times the fastest computer in the world). We are currently preparing a joint manuscript for publication where the results obtained on ARCHER will be used alongside with the results obtained on MDGRAPE-4. Julien Michel (Chemistry, Edinburgh) Free Energy Reproducibility Project Free energy reproducibility project between the Michel, Mobley, Roux groups and STFC. This makes use of FESetup which is CCPBioSim, but calculations have been executed on various HPC platforms, Hannes can clarify whether any of the systems used is within the remit of HECBioSim. Sarah Harris (Physics, Leeds), Charlie Laughton (Pharmacy, Nottingham) and Agnes Noy (Physics, York) In an international collaboration with the Institute for Research in Biomedicine in Barcelona, Noy, Harris and Laughton used ARCHER time obtained through the HecBioSim consortium to perform multiple 100ns molecular dynamics (MD) simulations of DNA minicircles containing ~100 base pairs as part of the validation suite for the new BSC1 nucleic acid forcefield, see: Ivani I., Dans P. D., Noy A., Perez A., Faustino I., Hospital A., Walther J., Andrio P., Goni R., Portella G., Battistini F.,Gelpi J. L. Gonzalez C., Vendruscolo M., Laughton C. A., Harris S. A. Case D. A. & Orozco M. "Parmbsc1: a refined force field for DNA simulations" Nat. Methods 13, 55, 2015, doi:10.1038/nmeth.3658 Jon Essex (Chemistry, Southampton) Development and testing of hybrid coarse-grain/atomistic model of membrane systems. ARCHER and the consortium were instrumental in providing the computing time necessary to complete this work. The work was performed by a research fellow in my group, who has subsequently taken up an academic post in Sweden, where he is continuing to develop this methodology. Publication: All-atom/coarse-grained hybrid predictions of distributioncoefficients in SAMPL5 Samuel Genheden1, Jonathan W. Essex, J Comput Aided Mol Des (2016) 30:969-976 DOI 10.1007/s10822-016-9926-z IP and other industrial engagement, or translation, which has benefited from HECBioSim international collaborations Collaboration Dr Samuel Genheden, University of Gothenburg - see above International activities (e.g. workshops) that have benefited from HECBioSim The work performed with Sam resulted in an successful eCSE application for development work on the LAMMPS software. This is an international simulation package run out of Sandia labs in the US. Through this eCSE application we were able to update the rotational integrator and improve the load balancing for our hybrid simulation methodology. These developments have been incorporated in the latest release versions of the code. An ARCHER training webinar resulted from this work. Training activities see above - ARCHER training webinar on our developments within LAMMPS Software development see above - code modifications in LAMMPS which either have been, or will be, in the release version of the code Advantages you see of the consortium (e.g. could be ability to pursue project quickly; develop collaborations) resources to run the sort of large-scale calculations we need Michelle Sahai (Department of life Sciences, Roehampton) The publication I added on ResearchFish has international co-authors. Combined in vitro and in silico approaches to the assessment of stimulant properties of novel psychoactive substances - The case of the benzofuran 5-MAPB. Sahai MA, Davidson C, Khelashvili G, Barrese V, Dutta N, Weinstein H, Opacka-Juffry J. Prog Neuropsychopharmacol Biol Psychiatry. (2016) 75:1-9. doi: 10.1016/j.pnpbp.2016.11.004. co-authors affiliations include: Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University (WCMC), New York, NY, 10065, USA and HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute of Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, NY, 10065, USA. Author contribution: CD, MAS, HW and JOJ were responsible for the study concept and design. CD and VB collected and interpreted the voltammetry data. JOJ and ND conducted the ligand binding experiments and ND analysed the data. MAS (ARCHER user) and GK performed the molecular modelling studies and interpreted the findings. CD, MAS, GK and JOJ drafted the manuscript. All authors critically reviewed the content and approved the final version for publication. Edina Rosta (Computational Chemistry, Kings College London) International collaborations I have several international collaborators with joint computational/experimental projects. For their success the HECBioSim computer time was essential: • Prof. Beata Vertessy, Budapest Technical University, Hungary JACS 2016 138 (45), 15035-15045 • Profs. Walter Kolch, Vio Buchete and Boris Kholodenko, UCD, Ireland Angewandte 55 (3), 983-986, 2016 (this may have been reported previously) PLOS Computational Biology 12 (10), e1005051, 2016 J Phys Chem Letters 7 (14), 2676-2682, 2016 • Jose Maria Lluch, Angels Gonzalez, Autonomous University of Barcelona, Spain JCTC 12 (4), 2079-2090, 2016 Other international activities Free energy and molecular kinetics workshop with Frank Noe's group (Free University of Berlin) and Vio Buchete (UCD, Dublin). Maybe this should be for training activities? Following the workshop, Erasmus students apply to visit my group. Phil Biggin (Biochemistry, Oxford) 2 and 4 were with colleagues from McGill (Brown PM, Aurousseau MR and Bowie) and 3 was with colleagues from Denmark (Braun and Pless) 2. Kainate receptor pore-forming and auxiliary subunits regulate channel block by a novel mechanism. Brown PM, Aurousseau MR, Musgaard M, Biggin PC, Bowie D. J Physiol. 2016 Apr 1;594(7):1821-40. doi: 10.1113/JP271690. 3. Role of an Absolutely Conserved Tryptophan Pair in the Extracellular Domain of Cys-Loop Receptors. Braun N, Lynagh T, Yu R, Biggin PC, Pless SA. ACS Chem Neurosci. 2016 Mar 16;7(3):339-48. doi: 10.1021/acschemneuro.5b00298. 4. Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes. Dawe GB, Musgaard M, Aurousseau MR, Nayeem N, Green T, Biggin PC, Bowie D. Neuron. 2016 Mar 16;89(6):1264-76. doi: 10.1016/j.neuron.2016.01.038. Richard Henchman I have an international collaboration with Professor Franke Grater at the University of Heidelberg on entropy theory for biomolecular systems. Syma Khalid (Chemistry, Southampton) Collaboration with Singapore National Center for Biotechnology. Contributions to CECAM workshops Other Highlights for the Current Reporting Period: Please provide details of any other significant highlights from the reporting period that are not captured elsewhere in the report. Professor Adrian Mullholland organised and chaired the Computational Chemistry, Gordon Research Conference, Girona, Spain 24th - 29th July 2016. The theme of the 2016 Computational Chemistry GRC was "Theory and Simulation Across Scales in Molecular Science". It focused on method development and state-of-the-art applications across computational molecular science, and encouraged cross-fertilization between areas. The conference was oversubscribed, with attendees from industry and academia. The meeting received a High-Performance Rating, and was commended for the assessment that 95% of conferees rated this meeting "above average" on all evaluation areas (science, discussion, management, atmosphere and suitability). HEC Consortia Model: Over the coming months EPSRC will be looking at the future of the HEC Consortia model and potential future funding. We would like to use this opportunity to ask the Consortia Chairs for input: • What are the key benefits that your community have experienced through the existence of the HEC Consortia? • What elements of the financial support provided by the HEC Consortium's grant have worked well and what could be improved in the future? We aim to expand the breadth of the work of the Consortium focusing on cutting-edge applications, and building collaborations with experiments and industry, to achieve maximum impact from ARCHER use. We discussed Grand Challenges at our most recent Management Group meeting. In December 2015, and have identified several to follow up as strategic priorities. We aim to tackle and support large-scale grand challenge applications in biomolecular science, in areas such as antimicrobial resistance, membrane dynamics, drug design and synthetic biology. One specific theme with potentially high impact in drug discovery is large -scale comparative investigation of allosteric regulation in different superfamilies of proteins (e.g. PAS domain containing proteins, tyrosine kinases, etc.). The major impact will be in the identification of novel selective therapeutic molecules with limited adverse side effects. As a Consortium, we intend to develop and apply novel computational approaches for the rational design of allosteric regulators of hitherto 'undruggable' targets. Many of the targets emerging from large-scale genetic screening are deemed undruggable due to the difficulty of designing drug-like modulators that bind to their catalytic sites. It is increasingly clear that these targets might be effectively targeted by designing drugs that bind to protein-protein interfaces and allosteric sites. To do that, however, new rational design strategies, based on an in-depth knowledge of protein dynamics and advanced modelling and new simulation techniques are required. Other challenging frontier areas include dynamics of motor proteins; prediction of the effects of pathogenic mutations on protein function. The accurate prediction of free energy of binding is still in its infancy and needs much further investigation. Finally, kinetics of biomolecular reactions will become the next big topic. It is clear that high end computing resource can provide the necessary power and capability to provide inroads into this vital area. This is important because it is becoming increasingly apparent that kinetics of drug binding is a key factor that the pharmaceutical sector should really be looking at in terms of a major dictator of potency. HECBioSim is now well established, supporting work of many groups across the UK in the growing field of biomolecular simulation. We benefit from an Advisory Group containing members from industry, as we as international biomolecular simulation experts and experimental scientists. The Advisory Board was expanded and refreshed for the renewal and consists of: Dr. Nicolas Foloppe (Vernalis plc, Chair); Dr. Colin Edge (GlaxoSmithKline); Dr. Mike King (UCB Pharmaceuticals); Dr. Mike Mazanetz (Evotec AG); Dr. Garrett Morris (Crysalin Ltd.); Dr. Gary Tresadern (Johnson and Johnson Pharmaceuticals); Dr. Richard Ward (AstraZeneca); Prof. Modesto Orozco (IRB, Barcelona); Prof. Tony Watts, (Oxford, NMR); Dr. Pete Bond (A*STAR Bioinformatics Institute Singapore). We aim to foster industrial collaborations and collaborations with experimentalists (e.g. joint workshops with CCPN, Institute of Physics (Sarah Harris, Leeds Physics); see e.g. case studies. A particular theme for strategic development will be multiscale modelling, building on collaborations between several groups in the Consortium and the other CCPs. This theme reflects the inclusive and forward looking philosophy of HecBioSim, which is a community open to new ideas, keen to develop new methods, and ultimately to use HEC to drive exciting new science. The Consortium model allows new collaborations to develop. The recent reduction in time allocated to HECBioSim has meant that we can support fewer projects. There is significantly more demand for computer time than we can accommodate through our current allocation. We intend to work with Tier 2 Centres to explore possibilities for applications, and e.g. to test emerging architectures for biomolecular simulation. Edina Rosta (Computational Chemistry, Kings College London) comments: "HECBioSim enables my group to perform biomolecular simulations at the high standards required for JACS, Angewandte, etc. Without this consortium I would not be able to perform the necessary calculations leading to publishable work in top journals as our local university resources are limited and the hpc systems are not well maintained". Regarding financial support: the administrative support provided via the consortium grant is essential to the functioning of HECBioSim. This role is currently undertaken by Simone Breckell who not only administers, allocates time to projects and arranges panel meetings but has also done a fantastic job collating the extensive information for this EPSRC report. 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? Yes  
Impact HECBioSim, the UK HEC Biomolecular Simulation Consortium, was established in March 2013, and works closely with and complements CCP-BioSim (the UK Collaborative Computational Project for Biomolecular Simulation at the Life Sciences Interface). Most of the members of the Consortium are experienced users of high end computing. Biomolecular simulations are now making significant contributions to a wide variety of problems in drug design and development, biocatalysis, bio and nano-technology, chemical biology and medicine. The UK has a strong and growing community in this field, recognized by the establishment in 2011 by the EPSRC of CCP-BioSim (ccpbiosim.ac.uk), and its renewal in 2015. There is a clear, growing and demonstrable need for HEC in this field. Members of the Consortium have, for example, served on the HECToR and ARCHER Resource Allocation Panel. The Consortium welcomes members across the whole biomolecular sciences community, and we are currently (and will remain) open to new members (unlike some consortia). Since establishing the Consortium, several new members (FLG, DH, ER) have joined the Management Group. Many of the projects awarded ARCHER time under the Consortium do not involve CCP-BioSim or HECBioSim Management Group members, demonstrating the openness of HECBioSim and its support of the biomolecular simulation community in the UK. A number of other researchers have joined and it is our expectation that other researchers will join HECBioSim in the future. We actively engage with structural and chemical biologists and industrial researchers. We foster interactions between computational, experimental and industrial scientists (see the example case studies; members of the Consortium have excellent links with many pharmaceutical, chemical and biotechnology companies). Details of HECBioSim are available via our webpages at: http://www.hecbiosim.ac.uk Applications are made through the website http://www.hecbiosim.ac.uk and reviewed at one of the series of regular panel meetings. A list of successful HECtime allocations on ARCHER is available at:http://www.hecbiosim.ac.uk/applications/successfulprojects All proposals are of course subject to scientific and technical review, but we have the philosophy of supporting the best science to deliver the highest impact, rather than focusing on supporting development of a couple of codes. An allocation panel (with changing membership) meets twice yearly to judge proposals and requests for AUs; projects are assessed competitively: any groups in the UK can apply. All submitted proposals receive constructive feedback from the allocation panel. The HECBioSim website also provides forums for the biomolecular simulation community, a wiki hosting useful how-tos and user guides, and software downloads (currently FESetup and Longbow). Our lead software development project between Nottingham (Charlie Laughton and Gareth Shannon) and Daresbury (James Gebbie), we have developed a remote job submission tool, 'Longbow' (see below). The tool is designed to reproduce the look and feel of local MD packages, but to stage data and submit jobs to a large HPC resource, such as ARCHER, in a manner invisible to the user. Workshops and New Opportunities No more than half a page detailing upcoming workshops and meetings. Also include discussion of other areas which are potentially of interest to other HEC Consortia and opportunities for cross CCP /HEC working. Workshops are listed below and can be found on the HECBioSim Website We work closely with CCP-BioSim, for example in organizing training workshops and meetings. Our activities are outlined at www.hecbiosim.ac.uk Examples of forthcoming meetings include: Computational Molecular Science 2017 - on Sunday 19 March 2017 17th European Seminar on Computational Methods in Quantum Chemistry - on Tuesday 11 July 2017 Frontiers of Biomolecular Simulation Southampton, September 2016 Issues and Problems Short discussion of any issues or problems that the HEC Consortium faces including issues with the ARCHER service, funding, management of allocation and staffing. This is also a good opportunity to highlight to the SLA committee any issues that the Consortium may have experienced with their SLA support during the reporting period. Details of SLA activities are given in the SLA report. Dr. James Gebbie provides support to HECBioSIm through the SLA. He has been very helpful in the construction of the HECBioSim webpages (hecbiosim.ac.uk). James also worked with Dr. Gareth Shannon on the development of Longbow (See above). In the past year, members of the Consortium faced some queuing problems; close to the end of the first allocation period in particular, there were long queuing times, which led to problems in completing jobs and using allocated time. Throughput has been a real problem in the past few months. Membership Please provide a full list of existing members and their institutions, highlighting any new members that have joined the consortium during the reporting period. If available please provide information on the number of distinct users that have accessed ARCHER via the Consortium during this reporting period. Below is a list of PIs with HECBioSim projects in the current reporting period: Agnes Noy, University of York - new to this reporting period Alessandro Pandini, Brunel University London Arianna Fornili, Queen Mary University of London Cait MacPhee, University of Edinbrurgh - new to this reporting period Charlie Laughton, University of Nottingham Clare-Louise Towse, University of Bradford - new to this reporting period D Flemming Hansen, University College London - new to this reporting period David Huggins, Aston University Edina Rosta, King's College London Francesco Gervasio, University College London Ian Collinson, University of Bristol - new to this reporting period Irina Tikhonova, Queen's University Belfast Jiayun Pang, University of Greenwich Jonathan Doye, University of Oxford Julien Michel, University of Edinburgh Mario Orsi, UWE Bristol Michele Vendruscolo, University of Cambridge Michelle Sahai, University of Roehampton Philip Biggin, University of Oxford Richard Sessions, University of Bristol Stephen Euston, Heriot-Watt University Syma Khalid, University of Southampton PIs in HECBioSIm outside of current allocation period Peter Bond, University of Cambridge Richard Bryce, University of Manchester Juan Antonio Bueren-Calabuig, University of Edinburgh Christo Christov, Northumbria University Anna K Croft, University of Nottingham Jonathan Essex, University of Southampton Robert Glen, University of Cambridge Sarah A Harris, University of Leeds Jonathan Hirst, University of Nottingham Douglas Houston, University of Edinburgh Dmitry Nerukh, Aston University Andrei Pisliakov, University of Dundee Mark Sansom, University of Oxford Marieke Schor, University of Edinburgh Gareth Shannon, University of Nottingham Tatyana Karabencheva-Christova, Northumbria University There are currently 164 members of HECBioSim (i.e. users of HECBioSIm ARCHER time), included the above PIs. 20 new users have been added since January 2016. World class and world leading scientific output: ARCHER should enable high quality and world-leading science to be delivered. This should generate high impact outputs and outcomes that increase the UK's position in world science. • If all the publications relating to the work of the Consortium for this reporting period have been added to ResearchFish / will be added to ResearchFish by the end of the ResearchFish reporting exercise, please indicate this below. • If submission of a full list of publications to the Consortium record/s in ResearchFish has not been possible for this reporting period please provide a list of publications that have resulted from work performed on ARCHER by the Consortium during this reporting period (this can be included as a separate attachment). • For the reporting period please provide a bullet pointed list of key / important research findings that has resulted from work performed on ARCHER by the Consortium. Please reference any related publications. • For the reporting period please include a bullet pointed list of any relevant press announcements and other communications of significance to an international community. All publications can be found in ResearchFish, and have been added by individual researchers. A selection of illustrative highlights are provided below: Julien Michel (University of Edinburgh) New molecular simulation methods have enabled for the first time a complete description of the interactions of several drug-like small molecules with an intrinsically disordered region of the oncoprotein MDM2, as well as the effect of post-translational modifications on the dynamics of this protein. The results obtained suggest new medicinal chemistry strategies to achieve potent and selective inhibition of MDM2 for cancer therapies. Publication: Elucidation of Ligand-Dependent Modulation of Disorder-Order Transitions in the Oncoprotein MDM2 http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004282 Impact of Ser17 Phosphorylation on the Conformational Dynamics of the Oncoprotein MDM2 http://pubs.acs.org/doi/abs/10.1021/acs.biochem.6b00127 An outreach document is being prepared by EPCC to showcase a lab project on isoform selective inhibition that has benefited from both HECBioSim and EPCC ARCHER allocations. Syma Khalid (Chemistry, Southampton) Publication: OmpA: A Flexible Clamp for Bacterial Cell Wall Attachment Samsudin F, Ortiz-Suarez ML, Piggot TJ, Bond PJ, Khalid S (2016). "OmpA: a Flexible Clamp for Bacterial Cell Wall Attachment", Structure, 24(12):2227-2235 With Singapore National Center for Biotechnology. Sarah Harris (Physics, Leeds) In collaboration with the experimental biochemistry group lead by Radford at Leeds, Sarah Harris used ARCHER time to show how chaperones help outer membrane proteins to fold, see: Schiffrin B, Calabrese AN, Devine PWA, Harris SA, Ashcroft AE, Brockwell DJ, Radford SE "Skp is a multivalent chaperone of outer-membrane proteins" Nature Structural and Molecular Biology 23 786-793, 2016. DOI:10.1038/nsmb.3266 Michelle Sahai (Department of Life Sciences, Roehampton) Publication: Combined in vitro and in silico approaches to the assessment of stimulant properties of novel psychoactive substances - The case of the benzofuran 5-MAPB. Progress in Neuro-Psychopharmacology and Biological Psychiatry 75, Pages 1-9 (2017) https://www.ncbi.nlm.nih.gov/pubmed/27890676 Phil Biggin (Biochemistry, Oxford) Outputs that have used HECBioSim time: 1. Steered Molecular Dynamics Simulations Predict Conformational Stability of Glutamate Receptors. Musgaard M, Biggin PC. J Chem Inf Model. 2016 Sep 26;56(9):1787-97. doi: 10.1021/acs.jcim.6b00297. 2. Kainate receptor pore-forming and auxiliary subunits regulate channel block by a novel mechanism. Brown PM, Aurousseau MR, Musgaard M, Biggin PC, Bowie D. J Physiol. 2016 Apr 1;594(7):1821-40. doi: 10.1113/JP271690. 3. Role of an Absolutely Conserved Tryptophan Pair in the Extracellular Domain of Cys-Loop Receptors. Braun N, Lynagh T, Yu R, Biggin PC, Pless SA. ACS Chem Neurosci. 2016 Mar 16;7(3):339-48. doi: 10.1021/acschemneuro.5b00298. 4. Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes. Dawe GB, Musgaard M, Aurousseau MR, Nayeem N, Green T, Biggin PC, Bowie D. Neuron. 2016 Mar 16;89(6):1264-76. doi: 10.1016/j.neuron.2016.01.038. Covered by 7 news outlets: I. Health Canal (http://www.healthcanal.com/brain-nerves/70646-what-makes-the-brain-tick-so-fast.html) II. Health Medicine Network (http://healthmedicinet.com/i/scientists-reveal-how-the-brain-processes-information-with-lightning-speed/) III. News Medical (http://www.news-medical.net/news/20160227/Scientists-reveal-how-the-brain-processes-information-with-lightning-speed.aspx) IV. Wired (http://www.wired.co.uk/article/what-we-learned-about-the-brain-this-week-3) V. Alpha Galileo (http://www.alphagalileo.org/ViewItem.aspx?ItemId=161473&CultureCode=en) VI. Science Daily (https://www.sciencedaily.com/releases/2016/02/160225140254.htm) VII. Eureka Alert (https://www.eurekalert.org/pub_releases/2016-02/mu-wmt022516.php) Recommended by F1000 Prime: http://f1000.com/prime/726180600. 5. Accurate calculation of the absolute free energy of binding for drug molecules. Aldeghi M, Heifetz A, Bodkin MJ, Knapp S, Biggin PC. Chem Sci. 2016 Jan 14;7(1):207-218. Arianna Fornili (Biological and Chemical Sciences, Queen Mary University of London) Publication: Fornili, E. Rostkova, F. Fraternali, M. Pfuhl: Effect of RlC N-Terminal Tails on the Structure and Dynamics of Cardiac Myosin. Biophysical J. 110 (2016) 297A. More in preparation. Dmitry Nerukh (Engineering and Applied Science, Aston University) Important research findings: Distribution of ions inside a viral capsids influences the stability of the capsid Edina Rosta (Computational Chemistry, Kings College London) Highlighted publication: We have a joint experimental paper with the Vertessy group in JACS where we identified a novel arginine finger residue in dUTPase enzymes, and described the mechanism of action for this residue using crystallographic data, biochemical experiments, MD and QM/MM simulations thanks to HECBioSim. http://pubs.acs.org/doi/abs/10.1021/jacs.6b09012 Press release: Our joint paper with Jeremy Baumberg's group in Cambridge was published in Nature. http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_13-6-2016-16-52-4 Greater scientific productivity: As well as speed increases, the optimisation of codes for the ARCHER machine will enable problems to be solved in less time using fewer compute resources. • For the reporting period please provide a brief update on the progress of software development activities associated with the Consortium and the impact this has had on Consortium members and the broader research community. Our lead software development project between Nottingham (Charlie Laughton and Gareth Shannon) and Daresbury (James Gebbie), we have developed a remote job submission tool, 'Longbow' (see below). The tool is designed to reproduce the look and feel of local MD packages, but to stage data and submit jobs to a large HPC resource such as ARCHER in a manner invisible to the user. An open beta version was released unrestricted to the community in March 2015 (http://www.hecbiosim.ac.uk/longbow and via PyPI https://pypi.python.org ) with ~100 downloads. Functionality includes native support for biosimulation packages AMBER, CHARMM, GROMACS, LAMMPS and NAMD, native support for jobs on ARCHER, native support for jobs running on PBS and LSF schedulers, and support for three different job types (single, ensembles and multiple jobs). The software is written both as an application for users and an API for developers. CCP-EM have integrated Longbow into their developmental GUI, and shortly FESetup will ship with native support for job submission using Longbow. We are currently in talks with ClusterVision with respect to them distributing Longbow to their user base as a user friendly way for novices to interact with their systems. Longbow Longbow has been growing in popularity both amongst researchers within the biosimulation field and those in other fields. In this reporting period there have been five new releases of Longbow delivering a plethora of user requested features and bug fixes. Some of the key developments are summarised below: • Implemented a Recovery mode - Should the event happen that Longbow crashes or the system in which Longbow is controlling jobs from powers down. The user can now reconnect to the crashed session and carry on as if nothing happened. • Sub-Queuing - More and more system administrators are setting limits not just on the number of simulations that can run, but also on the number of jobs that can go into the queue. Longbow can now automatically detect this and implement its own queue feeding jobs into the system queue as slots open up. • Dis-connectible/Re-connectible Longbow sessions - A user can now launch Longbow to fire off all jobs and then disconnect, at a later date the user can re-establish the connection and download all results (no need for persistent connections anymore) • Ability to include scripts in the Longbow generated submit files. • Numerous stability, performance and bug fixes Longbow continues to be the submission engine that is used under the hood of the CCP-EM toolkit FLEX-EM. There are several other interesting projects that are making use of Longbow. A project by the energy efficient computing group (Hartree Center) are currently integrating Longbow with CK, a crowd sourced compilation optimisation tool aimed at finding efficient compilation configuration. A project by the Applications performance engineering group (Hartree Center) are currently integrating longbow into Melody, a runtime optimisation tool aimed at optimising runtime configuration of simulations. A project by the computational biology group (Hartree Center) an automated setup, launch and analysis platform for MD on protein-membrane simulations. Metrics Downloads (HECBioSim) 985 Downloads (PyPi) 3456 Increasing the UK's CSE skills base (including graduate and post doctorate training and support): This builds on the skills sets of trained people in HPC, both in terms of capacity and raising the overall skill level available to the sector. • For the reporting period please provide information on the number of PhDs and Post-Docs that have been trained in the use of ARCHER as a result of work relating to the Consortium. • For the reporting period please provide a bullet pointed list of training activities undertaken by the Consortium, providing information on the target audience and level of attendance. 125 PhD and PDRAs have been trained and have used ARCHER through HECBioSim. In the past 6 months alone that has included: PhD students: Marc Dämgen, University of Oxford Laura Domicevica, University of Oxford Matteo Aldeghi, University of Oxford Shaima Hashem, Queen Mary University of London Ruth Dingle, University College London Lucas Siemons, University College London Elvira Tarasova, Aston University Vladimiras Oleinikovas, University College London Havva Yalinca, University College London Daniel Moore, Queen's University Belfast Aaron Maguire, Queen's University Belfast Maxime Tortora, University of Oxford Michail Palaiokostas, UWE Bristol Wei Ding, UWE Bristol Ganesh Shahane, UWE Bristol Pin-Chia Hsu, University of Southampton Damien Jefferies, University of Southampton PDRA: Maria Musgaard, University of Oxford Teresa Paramo, University of Oxford Marieke Schor, University of Edinbrurgh Antonia Mey, University of Edinbrurgh Ioanna Styliari, University of Nottingham Ivan Korotkin, Aston University Silvia Gomez Coca, King's College London Giorgio Saladino, University College London Federico Comitani, University College London Robin Corey, University of Bristol Jordi Juarez-Jimenez, University of Edinburgh Predrag Kukic, University of Cambridge Giulia Tomba, University of Cambridge Deborah Shoemark, University of Bristol Georgios Dalkas, Heriot-Watt University Robin Westacott, Heriot-Watt University Firdaus Samsudin, University of Southampton Agnes Noy, University of Leeds (now EPSRC fellow at York). Please see below details of the training week held in June 2016 at the University of Bristol. 170 delegates attending the training which ran over 5 days. There is course content available on the HECBioSim Workshop Page CCPBioSim Training Week - Day 5: QM/MM enzyme reaction modelling - on Friday 10 June 2016 CCPBioSim Training Week - Day 4: Monte Carlo Methods for Biomodelling - on Thursday 09 June 2016 CCPBioSim Training Week - Day 3: Python for Biomodellers and FESetup - on Wednesday 08 June 2016 CCPBioSim Training Week - Day 2: Running and analysing MD simulations - on Tuesday 07 June 2016 CCPBioSim Training Week - Day 1: Enlighten: Tools for enzyme-ligand modelling - on Monday 06 June 2016 Past Workshops and Conferences: AMOEBA advanced potential energies workshop - on Friday 09 December 2016 Intel Training Workshop (Parallel programming and optimisation for Intel architecture) - on Wednesday 30 November 2016 3rd Workshop on High-Throughput Molecular Dynamics (HTMD) 2016 - on Thursday 10 November 2016 Free Energy Calculation and Molecular Kinetics Workshop - on Tuesday 13 September 2016 Going Large: tools to simplify running and analysing large-scale MD simulations on HPC resources - HECBioSim - on Wednesday 16 December 2015 This 1 day workshop dealt with Longbow, a Python tool created by HECBioSim consortium that allows use of molecular dynamics packages (AMBER, GROMACS, LAMMPS, NAMD) with ease from the comfort of the desktop, and pyPcazip, a flexible Python-based package for the analysis of large molecular dynamics trajectory data sets. Richard Henchman ( Chemistry, Manchester) I lectured on the CCP5 Summer School in 2015 in Manchester and 2016 in Lancaster for the Advanced Topic Biomolecular Simulation drawing on CCPBiosim training materials. Sarah Harris (Physics, Leeds) Agnes Noy Agnes Noy was trained to use ARCHER independently which helped her to obtain an Early-career EPSRC fellowship. The fellowship grant follows the study of supercoiling DNA by modelling (further funding) and introduces a new member to the community (grant is EPSRC (EP/N027639/1)). Increased impact and collaboration with industry: ARCHER does not operate in isolation and the 'impact' of ARCHER's science is converted to economic growth through the interfaces with business and industry. In order to capture the impacts, which may be economic, social, environmental, scientific or political, various metrics may be utilised. • For the reporting period please provide where possible information on Consortium projects that have been performed in collaboration with industry, this should include: o Details of the companies involved. o Information on the part ARCHER and the Consortium played. o A statement on the impact that the work has / is making. o If relevant, details of any in kind or cash contributions that have been associated with this work. • For the reporting period include a list of Consortium publications that have industrial co-authorship. • For the reporting period please provide details of the any other activities involving industrial participation e.g. activities involving any Industrial Advisory panels, attendance / participation in workshops and Consortium based activities. Examples of industrial engagement through HECBioSim include: Syma Khalid (Computational Biophysics, Southampton) Collaboration with Siewert-Jan Marrink (Netherlands) and Wonpil Im(USA) - paper is being written at the moment - also we have developed and tested the following computational tool as part of this project: http://www.charmm-gui.org/?doc=input/membrane We have signed an NDA with a company developing antibiotics (Auspherix) based on work published in Samsudin et al, Structure, 2016. The company provide us with experimental data and crucially the structures of their potential drug molecules, and we work out how they interact with the bacterial membrane. Press releases https://www.sciencedaily.com/releases/2016/11/161121094122.htm ARCHER time we got from HECBioSim was essential for this project. These are large simulations that are very computationally demanding. Julien Michel (Chemistry, Edinburgh) Industrial collaborations that have benefited from HECBioSim UCB was a project partner of EPSRC-funded research in the Michel lab on modelling binding of ligands to flexible proteins. HECBioSim supported the research via allocation of computing time on ARCHER. The work has been published. Impact of Ser17 phosphorylation on the conformational dynamics of the oncoprotein MDM2 Bueren-Calabuig, J. A. ; Michel, J. Biochemistry, 55 (17), 2500-2509, 2016 Elucidation of Ligand-Dependent Modulation of Disorder-Order Transitions in the Oncoprotein MDM2 Bueren-Calabuig, J. A. ; Michel, J. PLoS Comput. Biol. , 11(6): e1004282, 2015 International activities I represented HECBioSim at the MolSSI conceptualisation workshop in Houston (October 2016). Arianna Fornili (School of Biological and Chemical Sciences, Queen Mary University of London) This project is done in collaboration with experimental (NMR and SAXS) partners at King's College London (Dr. Mark Pfuhl and Dr. Elena Rostkova), with the final aim of providing a complete molecular model of how muscle contraction is regulated in the heart. Francesco Gervasio (Chemistry, UCL) A new collaboration with UCB on developing new approaches to sample cryptic binding sites of pharmaceutical interest was started. UCB co-sponsored a BBSRC-CASE PhD studentships. The code development and its application to interesting targets was made possible by the access to Archer. Phil Biggin (Biochemistry, Oxford) The following has industrial partners as co-authors: Accurate calculation of the absolute free energy of binding for drug molecules, Aldeghi M, Heifetz A, Bodkin MJ, Knapp S, Biggin PC. Chem. Sci., 2016,7, 207-218 doi: 10.1039/C5SC02678D. The GLAS scoring module for gromacs has yet to be implemented but that would also constitute industrial activity. Richard Henchman (Chemistry, Manchester) Industrial Collaboration I have one publication with an industrial co-author (Evotec), which Julien Michel is part of as well. Assessment of hydration thermodynamics at protein interfaces with grid cell theory, G. Gerogiokas, M. W. Y. Southey, M. P. Mazanetz, A. Heifetz, M. Bodkin, R. J. Law, R. H. Henchman and J. Michel, J. Phys. Chem. B, 2016, 120, 10442-10452. Strengthening of UK's international position: The impacts of ARCHER's science extend beyond national borders and most science is delivered through partnerships on a national or international level. • For the reporting period please provide a bullet pointed list of projects that have involved international collaboration. For each example please provide a brief summary of the part that ARCHER and the Consortium have played. • For the reporting period please provide a list of consortium publications with international co-authorship. • For the reporting period please detail any other international activities that the Consortium might be involved in (workshops, EU projects etc.). Examples of HECBioSim international engagement include: Michelle Sahai (Department of Life Sciences, Roehampton) Combined in vitro and in silico approaches to the assessment of stimulant properties of novel psychoactive substances - The case of the benzofuran 5-MAPB. Sahai MA, Davidson C, Khelashvili G, Barrese V, Dutta N, Weinstein H, Opacka-Juffry J. Prog Neuropsychopharmacol Biol Psychiatry. (2016) 75:1-9. doi: 10.1016/j.pnpbp.2016.11.004. co-authors affiliations include: Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University (WCMC), New York, NY, 10065, USA and HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute of Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, NY, 10065, USA. Author contribution: CD, MAS, HW and JOJ were responsible for the study concept and design. CD and VB collected and interpreted the voltammetry data. JOJ and ND conducted the ligand binding experiments and ND analysed the data. MAS (ARCHER user) and GK performed the molecular modelling studies and interpreted the findings. CD, MAS, GK and JOJ drafted the manuscript. All authors critically reviewed the content and approved the final version for publication. Dmitry Nerukh (Engineering and Applied Science, Aston University) Collaborations: • Prof. Makoto Taiji group (K-computer, MDGRAPE), Laboratory for Computational Molecular Design, Computational Biology Research Core, RIKEN Quantitative Biology Center (QBiC), Kobe, Japan • Prof. Reza Khayat group, City College of New York, United States • Prof. Artyom Yurov group, Immanuel Kant Baltic Federal University, Russian Federation • Prof. Nikolay Mchedlov-Petrosyan group, V.N. Karazin Kharkiv National University, Ukraine • Prof. Natalya Vaysfeld group, Odessa I.I.Mechnikov National University, Ukraine International activities: • International Workshop - Engineering bacteriophages for treating antimicrobial resistance using computational models. Dec. 2016, Aston University, UK Dmitry Nerukh group at Aston University collaborates with the group of Prof. Makoto Taiji (the deputy director of RIKEN Quantitative Biology Institute). Prof. Taiji group is the author and implementer of the fastest machine in the world for molecular dynamics simulations, MDGRAPE, as well as part of the team designing the K-computer and working on it (several times the fastest computer in the world). We are currently preparing a joint manuscript for publication where the results obtained on ARCHER will be used alongside with the results obtained on MDGRAPE-4. Julien Michel (Chemistry, Edinburgh) Free Energy Reproducibility Project Free energy reproducibility project between the Michel, Mobley, Roux groups and STFC. This makes use of FESetup which is CCPBioSim, but calculations have been executed on various HPC platforms, Hannes can clarify whether any of the systems used is within the remit of HECBioSim. Sarah Harris (Physics, Leeds), Charlie Laughton (Pharmacy, Nottingham) and Agnes Noy (Physics, York) In an international collaboration with the Institute for Research in Biomedicine in Barcelona, Noy, Harris and Laughton used ARCHER time obtained through the HecBioSim consortium to perform multiple 100ns molecular dynamics (MD) simulations of DNA minicircles containing ~100 base pairs as part of the validation suite for the new BSC1 nucleic acid forcefield, see: Ivani I., Dans P. D., Noy A., Perez A., Faustino I., Hospital A., Walther J., Andrio P., Goni R., Portella G., Battistini F.,Gelpi J. L. Gonzalez C., Vendruscolo M., Laughton C. A., Harris S. A. Case D. A. & Orozco M. "Parmbsc1: a refined force field for DNA simulations" Nat. Methods 13, 55, 2015, doi:10.1038/nmeth.3658 Jon Essex (Chemistry, Southampton) Development and testing of hybrid coarse-grain/atomistic model of membrane systems. ARCHER and the consortium were instrumental in providing the computing time necessary to complete this work. The work was performed by a research fellow in my group, who has subsequently taken up an academic post in Sweden, where he is continuing to develop this methodology. Publication: All-atom/coarse-grained hybrid predictions of distributioncoefficients in SAMPL5 Samuel Genheden1, Jonathan W. Essex, J Comput Aided Mol Des (2016) 30:969-976 DOI 10.1007/s10822-016-9926-z IP and other industrial engagement, or translation, which has benefited from HECBioSim international collaborations Collaboration Dr Samuel Genheden, University of Gothenburg - see above International activities (e.g. workshops) that have benefited from HECBioSim The work performed with Sam resulted in an successful eCSE application for development work on the LAMMPS software. This is an international simulation package run out of Sandia labs in the US. Through this eCSE application we were able to update the rotational integrator and improve the load balancing for our hybrid simulation methodology. These developments have been incorporated in the latest release versions of the code. An ARCHER training webinar resulted from this work. Training activities see above - ARCHER training webinar on our developments within LAMMPS Software development see above - code modifications in LAMMPS which either have been, or will be, in the release version of the code Advantages you see of the consortium (e.g. could be ability to pursue project quickly; develop collaborations) resources to run the sort of large-scale calculations we need Michelle Sahai (Department of life Sciences, Roehampton) The publication I added on ResearchFish has international co-authors. Combined in vitro and in silico approaches to the assessment of stimulant properties of novel psychoactive substances - The case of the benzofuran 5-MAPB. Sahai MA, Davidson C, Khelashvili G, Barrese V, Dutta N, Weinstein H, Opacka-Juffry J. Prog Neuropsychopharmacol Biol Psychiatry. (2016) 75:1-9. doi: 10.1016/j.pnpbp.2016.11.004. co-authors affiliations include: Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University (WCMC), New York, NY, 10065, USA and HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute of Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, NY, 10065, USA. Author contribution: CD, MAS, HW and JOJ were responsible for the study concept and design. CD and VB collected and interpreted the voltammetry data. JOJ and ND conducted the ligand binding experiments and ND analysed the data. MAS (ARCHER user) and GK performed the molecular modelling studies and interpreted the findings. CD, MAS, GK and JOJ drafted the manuscript. All authors critically reviewed the content and approved the final version for publication. Edina Rosta (Computational Chemistry, Kings College London) International collaborations I have several international collaborators with joint computational/experimental projects. For their success the HECBioSim computer time was essential: • Prof. Beata Vertessy, Budapest Technical University, Hungary JACS 2016 138 (45), 15035-15045 • Profs. Walter Kolch, Vio Buchete and Boris Kholodenko, UCD, Ireland Angewandte 55 (3), 983-986, 2016 (this may have been reported previously) PLOS Computational Biology 12 (10), e1005051, 2016 J Phys Chem Letters 7 (14), 2676-2682, 2016 • Jose Maria Lluch, Angels Gonzalez, Autonomous University of Barcelona, Spain JCTC 12 (4), 2079-2090, 2016 Other international activities Free energy and molecular kinetics workshop with Frank Noe's group (Free University of Berlin) and Vio Buchete (UCD, Dublin). Maybe this should be for training activities? Following the workshop, Erasmus students apply to visit my group. Phil Biggin (Biochemistry, Oxford) 2 and 4 were with colleagues from McGill (Brown PM, Aurousseau MR and Bowie) and 3 was with colleagues from Denmark (Braun and Pless) 2. Kainate receptor pore-forming and auxiliary subunits regulate channel block by a novel mechanism. Brown PM, Aurousseau MR, Musgaard M, Biggin PC, Bowie D. J Physiol. 2016 Apr 1;594(7):1821-40. doi: 10.1113/JP271690. 3. Role of an Absolutely Conserved Tryptophan Pair in the Extracellular Domain of Cys-Loop Receptors. Braun N, Lynagh T, Yu R, Biggin PC, Pless SA. ACS Chem Neurosci. 2016 Mar 16;7(3):339-48. doi: 10.1021/acschemneuro.5b00298. 4. Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes. Dawe GB, Musgaard M, Aurousseau MR, Nayeem N, Green T, Biggin PC, Bowie D. Neuron. 2016 Mar 16;89(6):1264-76. doi: 10.1016/j.neuron.2016.01.038. Richard Henchman I have an international collaboration with Professor Franke Grater at the University of Heidelberg on entropy theory for biomolecular systems. Syma Khalid (Chemistry, Southampton) Collaboration with Singapore National Center for Biotechnology. Contributions to CECAM workshops Other Highlights for the Current Reporting Period: Please provide details of any other significant highlights from the reporting period that are not captured elsewhere in the report. Professor Adrian Mullholland organised and chaired the Computational Chemistry, Gordon Research Conference, Girona, Spain 24th - 29th July 2016. The theme of the 2016 Computational Chemistry GRC was "Theory and Simulation Across Scales in Molecular Science". It focused on method development and state-of-the-art applications across computational molecular science, and encouraged cross-fertilization between areas. The conference was oversubscribed, with attendees from industry and academia. The meeting received a High-Performance Rating, and was commended for the assessment that 95% of conferees rated this meeting "above average" on all evaluation areas (science, discussion, management, atmosphere and suitability). HEC Consortia Model: Over the coming months EPSRC will be looking at the future of the HEC Consortia model and potential future funding. We would like to use this opportunity to ask the Consortia Chairs for input: • What are the key benefits that your community have experienced through the existence of the HEC Consortia? • What elements of the financial support provided by the HEC Consortium's grant have worked well and what could be improved in the future? We aim to expand the breadth of the work of the Consortium focusing on cutting-edge applications, and building collaborations with experiments and industry, to achieve maximum impact from ARCHER use. We discussed Grand Challenges at our most recent Management Group meeting. In December 2015, and have identified several to follow up as strategic priorities. We aim to tackle and support large-scale grand challenge applications in biomolecular science, in areas such as antimicrobial resistance, membrane dynamics, drug design and synthetic biology. One specific theme with potentially high impact in drug discovery is large -scale comparative investigation of allosteric regulation in different superfamilies of proteins (e.g. PAS domain containing proteins, tyrosine kinases, etc.). The major impact will be in the identification of novel selective therapeutic molecules with limited adverse side effects. As a Consortium, we intend to develop and apply novel computational approaches for the rational design of allosteric regulators of hitherto 'undruggable' targets. Many of the targets emerging from large-scale genetic screening are deemed undruggable due to the difficulty of designing drug-like modulators that bind to their catalytic sites. It is increasingly clear that these targets might be effectively targeted by designing drugs that bind to protein-protein interfaces and allosteric sites. To do that, however, new rational design strategies, based on an in-depth knowledge of protein dynamics and advanced modelling and new simulation techniques are required. Other challenging frontier areas include dynamics of motor proteins; prediction of the effects of pathogenic mutations on protein function. The accurate prediction of free energy of binding is still in its infancy and needs much further investigation. Finally, kinetics of biomolecular reactions will become the next big topic. It is clear that high end computing resource can provide the necessary power and capability to provide inroads into this vital area. This is important because it is becoming increasingly apparent that kinetics of drug binding is a key factor that the pharmaceutical sector should really be looking at in terms of a major dictator of potency. HECBioSim is now well established, supporting work of many groups across the UK in the growing field of biomolecular simulation. We benefit from an Advisory Group containing members from industry, as we as international biomolecular simulation experts and experimental scientists. The Advisory Board was expanded and refreshed for the renewal and consists of: Dr. Nicolas Foloppe (Vernalis plc, Chair); Dr. Colin Edge (GlaxoSmithKline); Dr. Mike King (UCB Pharmaceuticals); Dr. Mike Mazanetz (Evotec AG); Dr. Garrett Morris (Crysalin Ltd.); Dr. Gary Tresadern (Johnson and Johnson Pharmaceuticals); Dr. Richard Ward (AstraZeneca); Prof. Modesto Orozco (IRB, Barcelona); Prof. Tony Watts, (Oxford, NMR); Dr. Pete Bond (A*STAR Bioinformatics Institute Singapore). We aim to foster industrial collaborations and collaborations with experimentalists (e.g. joint workshops with CCPN, Institute of Physics (Sarah Harris, Leeds Physics); see e.g. case studies. A particular theme for strategic development will be multiscale modelling, building on collaborations between several groups in the Consortium and the other CCPs. This theme reflects the inclusive and forward looking philosophy of HecBioSim, which is a community open to new ideas, keen to develop new methods, and ultimately to use HEC to drive exciting new science. The Consortium model allows new collaborations to develop. The recent reduction in time allocated to HECBioSim has meant that we can support fewer projects. There is significantly more demand for computer time than we can accommodate through our current allocation. We intend to work with Tier 2 Centres to explore possibilities for applications, and e.g. to test emerging architectures for biomolecular simulation. Edina Rosta (Computational Chemistry, Kings College London) comments: "HECBioSim enables my group to perform biomolecular simulations at the high standards required for JACS, Angewandte, etc. Without this consortium I would not be able to perform the necessary calculations leading to publishable work in top journals as our local university resources are limited and the hpc systems are not well maintained". Regarding financial support: the administrative support provided via the consortium grant is essential to the functioning of HECBioSim. This role is currently undertaken by Simone Breckell who not only administers, allocates time to projects and arranges panel meetings but has also done a fantastic job collating the extensive information for this EPSRC report. 
URL http://www.hecbiosim.ac.uk
 
Title Bristol University uses Oracle Cloud Infrastructure to speed up smoking cessation drug discovery 
Description Scientists from the University of Bristol used Oracle Cloud Infrastructure to speed up research into how nicotine causes addiction by binding to specific receptors in the brain. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2019 
Provided To Others? Yes  
Impact Scientists at the University of Bristol have published research showing how nicotine affects receptors in the brain as part of an effort to design drugs that will help smokers to quit. They have done so using Oracle Cloud Infrastructure donated by the supplier and in collaboration with Achieve Life Sciences, a Seattle-based pharmaceutical company focused on the commercialisation of Cytisinicline, a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor in the human brain. According to the US National Institute on Drug Abuse, the majority of smokers would like to stop smoking, and each year around half try to quit permanently. Yet, only about 6% of smokers are able to quit in any given year. Smoking is the second most common cause of death worldwide. The paper that issued from the Bristol research, A general mechanism for signal propagation in the nicotinic acetylcholine receptor family, was published in the Journal of the American Chemical Society in December 2019. Two of the authors are from Oracle's Cloud Development Centre in Bristol, Phil Bates and Gerardo Viedma Nunez. Adrian Mulholland from the University of Bristol's Centre for Computational Chemistry was co-lead author on the paper, along with Richard Sessions, senior research fellow at the School of Biochemistry at Bristol. Mulholland told Computer Weekly: "Our work shows how nicotine exerts its effects on nicotinic acetylcholine receptors. Understanding this should help us design better smoking cessation aids." The study, led by led University of Bristol scientists but involving academics from other institutions, used Oracle's cloud infrastructure. The researchers used new computational simulation methods to conduct 450 assessments of the biochemistry associated with the binding of nicotine to a subtype of nicotinic acetylcholine receptors, a mechanism believed to be responsible for the highly addictive nature of the drug. "Each simulation takes eight hours to run on a single cloud node", said Mulholland. "If we had used our own high-performance computing facility, it would have taken 90 days to do what we did in five. "We are lucky at Bristol to have pretty good HPC resources, but what the Oracle Cloud enabled us to do was to run a new class of simulation - 'non-equilibrium' simulations, of which there are hundreds that have to be done in parallel. The Oracle Cloud enabled us to run them in a matter of weeks, whereas it would otherwise have taken us a year. "To understand why nicotine is so addictive, and to develop molecules to help people quit smoking, we need to understand how nicotine affects the nervous system. By harnessing the power of cloud computing, we can quickly observe how nicotine exerts its effects at the molecular level. This information can inform future drug development of new treatments for companies like Achieve." According to a press statement from Achieve Life Sciences, Oracle and Bristol, the university and the pharmaceutical firm have teamed up to "formulate molecules and potential treatments to combat addiction and neurological disorders based on smoking cessation compound in development, cytisinicline". Cytisinicline is, according to the statement, a "plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in smoking cessation by interacting with nicotine receptors in the brain by reducing the severity of nicotine withdrawal symptoms and by reducing the reward and satisfaction associated with smoking." The drug has been approved in Central and Eastern Europe for more than two decades, and has been used by "more than 20 million people", according to the press statement. The paper is one output of research originally funded by the EPSRC in 2016, with £724,000. Mulholland said the beauty of being able to use cloud computing for this sort of scientific research lies in its capacity to enable collaboration. "I'm a great believer in different sorts of scientists working together to get the best results. And that's not about computation in its own right, but as part of a product development programme," he said. "It's helping to inform what sort of molecules people might make to test as potential medicines. Being able to do the computational simulations fast enough so that scientists can design and adapt their experiments quickly should accelerate drug development. We couldn't have done this two years ago." The work brought together computational chemists, biochemists and research software engineers, working together to deploy the simulations of nicotine receptors. The computer simulations methodology used in this particular area of neuroscience could also, said Mulholland, be applied to the study of schizophrenia and Alzheimer's. 
URL https://www.computerweekly.com/news/252476773/Bristol-University-uses-Oracle-Cloud-Infrastructure-to...
 
Title SWISH a new Hamiltonian Replica Exchange-based computational algorithm 
Description We developed a novel and effective computational approach to predict cryptic binding sites on targets of pharmaceutical interest. 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? Yes  
Impact The method has been described in an high-impact publication (JACS) and in a number of high-profile blogs in drug discovery. The PI has been invited by Pfizer and other pharmaceutical companies to give talks about the method. 
 
Title SlimMD 
Description This tool is a repository for sharing molecular dynamics trajectories developed by Sarah Harris and James Gebbie-Rayet. Biomolecular simulations are extremely computationally expensive, and so consume lots of energy when they run. We therefore need to make best use of them to respect our environment, so please do share and cite! The material in SlimMD has a maximum file size of 1GB and standard file formats and names making it easy to download and use. 
Type Of Material Improvements to research infrastructure 
Year Produced 2021 
Provided To Others? Yes  
Impact No impact has been reported yet, but this is expected to help with training and introducing new people to computational biology. It will be particullarly helpful for students on short projects who do not have the time or resources to run expensive simulations. 
URL https://www.ccpbiosim.ac.uk/slimmd
 
Title A Multiscale Workflow for Modelling Ligand Complexes of Zinc Metalloproteins 
Description Representative MD trajectories, topologies and input files for the protein:ligand complexes presented in the paper Yang et al. J Chem. Inf. Model. 2021. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact Zinc metalloproteins are ubiquitous, with protein zinc centers of structural and functional importance, involved in interactions with ligands and substrates and often of pharmacological interest. Biomolecular simulations are increasingly prominent in investigations of protein structure, dynamics, ligand interactions, and catalysis, but zinc poses a particular challenge, in part because of its versatile, flexible coordination. A computational workflow generating reliable models of ligand complexes of biological zinc centers would find broad application. Here, we evaluate the ability of alternative treatments, using (nonbonded) molecular mechanics (MM) and quantum mechanics/molecular mechanics (QM/MM) at semiempirical (DFTB3) and density functional theory (DFT) levels of theory, to describe the zinc centers of ligand complexes of six metalloenzyme systems differing in coordination geometries, zinc stoichiometries (mono- and dinuclear), and the nature of interacting groups (specifically the presence of zinc-sulfur interactions). MM molecular dynamics (MD) simulations can overfavor octahedral geometries, introducing additional water molecules to the zinc coordination shell, but this can be rectified by subsequent semiempirical (DFTB3) QM/MM MD simulations. B3LYP/MM geometry optimization further improved the accuracy of the description of coordination distances, with the overall effectiveness of the approach depending upon factors, including the presence of zinc-sulfur interactions that are less well described by semiempirical methods. We describe a workflow comprising QM/MM MD using DFTB3 followed by QM/MM geometry optimization using DFT (e.g., B3LYP) that well describes our set of zinc metalloenzyme complexes and is likely to be suitable for creating accurate models of zinc protein complexes when structural information is more limited. 
URL https://data.bris.ac.uk/data/dataset/10p78zgsappbz226bzrdagabq9/
 
Title Atomic force microscopy and atomistic molecular dynamics simulation data to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. 
Description Simulations results and data source of Figures published on Nature Communications 2021 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact Available publicly. It is of interest of the research community 
URL https://springernature.figshare.com/articles/dataset/Atomic_force_microscopy_and_atomistic_molecular...
 
Title Evolution of dynamical networks enhances catalysis in a designer enzyme 
Description Data related to: "Evolution of dynamical networks enhances catalysis in a designer enzyme". H. Adrian Bunzel, J. L. Ross Anderson, Donald Hilvert, Vickery L. Arcus, Marc W. van der Kamp, Adrian J. Mulholland. Nature Chemistry 2021. MD Trajectories of a designed and evolved Kemp eliminase (1A53-2 and 1A53-2.5) in complex with a ground state (GS) or transition state (TS, TS2) model. The ligands are called GS1, TS1, and TS3 in the raw data. Cluster analysis of each trajectory, discriminating between an open (0) or closed (1) state for each frame. Pymol Sessions to reproduce Figures 1-3 of the paper. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact Activation heat capacity is emerging as a crucial factor in enzyme thermoadaptation, as shown by the non-Arrhenius behaviour of many natural enzymes. However, its physical origin and relationship to the evolution of catalytic activity remain uncertain. Here we show that directed evolution of a computationally designed Kemp eliminase reshapes protein dynamics, which gives rise to an activation heat capacity absent in the original design. These changes buttress transition-state stabilization. Extensive molecular dynamics simulations show that evolution results in the closure of solvent-exposed loops and a better packing of the active site. Remarkably, this gives rise to a correlated dynamical network that involves the transition state and large parts of the protein. This network tightens the transition-state ensemble, which induces a negative activation heat capacity and non-linearity in the activity-temperature dependence. Our results have implications for understanding enzyme evolution and suggest that selectively targeting the conformational dynamics of the transition-state ensemble by design and evolution will expedite the creation of novel enzymes. 
URL https://data.bris.ac.uk/data/dataset/l6hm9j11yil92bh9rvh27i7ge/
 
Title IHF bends and bridges DNA in a multiplicity of states 
Description A representative pdb for each of the 4 topological states IHF induces in linear DNA 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact Structures obtained from simulations publicly available 
URL https://pure.york.ac.uk/portal/en/datasets/ihf-bends-and-bridges-dna-in-a-multiplicity-of-states(0b6...
 
Title Ligand-induced unfolding mechanism of an RNA G-quadruplex 
Description These are the trajectories for unbiased simulations of PQS-18-1 and TMPyP4. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
URL https://zenodo.org/record/5594384
 
Title MemProtMD 
Description a datbase of all membrane protein structures and their interactions with lipids 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact Considerable interest and uptake by membrane protein structural biologists in academia and industry (pharma). 
URL http://memprotmd.bioch.ox.ac.uk
 
Title SWISH a new Hamiltonian Replica Exchange-based computational algorithm 
Description We developed a novel and effective computational approach to predict cryptic binding sites on targets of pharmaceutical interest. 
Type Of Material Computer model/algorithm 
Year Produced 2016 
Provided To Others? Yes  
Impact The method has been described in an high-impact publication (JACS) and in a number of high-profile blogs in drug discovery. The PI has been invited by Pfizer and other pharmaceutical companies to give talks about the method. 
 
Title Simulation of Functional Motions in Enzymes 
Description Data related to: "Structure and function in homodimeric enzymes: simulations of cooperative and independent functional motions". Wells SA, Van der Kamp MW, Mulholland AJ. PLOS ONE, 2015. Results from two different simulation methods, normal-mode biased geometric simulations of flexible motion and conventional molecular dynamics, as applied to two different homodimeric enzymes, the DcpS scavanger decapping enzyme and citrate synthase. 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact Large-scale conformational change is a common feature in the catalytic cycles of enzymes. Many enzymes function as homodimers with active sites that contain elements from both chains. Symmetric and anti-symmetric cooperative motions in homodimers can potentially lead to correlated active site opening and/or closure, likely to be important for ligand binding and release. Here, we examine such motions in two different domain-swapped homodimeric enzymes: the DcpS scavenger decapping enzyme and citrate synthase. We use and compare two types of all-atom simulations: conventional molecular dynamics simulations to identify physically meaningful conformational ensembles, and rapid geometric simulations of flexible motion, biased along normal mode directions, to identify relevant motions encoded in the protein structure. The results indicate that the opening/closure motions are intrinsic features of both unliganded enzymes. In DcpS, conformational change is dominated by an anti-symmetric cooperative motion, causing one active site to close as the other opens; however a symmetric motion is also significant. In CS, we identify that both symmetric (suggested by crystallography) and asymmetric motions are features of the protein structure, and as a result the behaviour in solution is largely non-cooperative. The agreement between two modelling approaches using very different levels of theory indicates that the behaviours are indeed intrinsic to the protein structures. Geometric simulations correctly identify and explore large amplitudes of motion, while molecular dynamics simulations indicate the ranges of motion that are energetically feasible. Together, the simulation approaches are able to reveal unexpected functionally relevant motions, and highlight differences between enzymes. 
URL http://data.bris.ac.uk/data/dataset/1klro7qjw27xi19qrcs1bb2nt6/
 
Title Simulations of circular RNAs from the Rolling Circle RNA synthesis 
Description All-atom trajectories from simulations done over the different stages of Rolling Circle RNA synthesis 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact None 
URL https://pure.york.ac.uk/portal/en/datasets/b92977bd-f016-4740-8b4a-f86c68d5eb2c
 
Title Simulations of supercoiled minicircles bound to IHF 
Description Trajectories for all-atom simulations pf DNA minicircles bound to the bacterial protein IHF 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact None 
 
Title agnesnoy/SerraLINE: SerraLINE v1.0 
Description Version utilized in the paper: ALB Pyne, A Noy, K Main, V Velasco-Berrelleza, MM Piperakis, LA Mitchenall, FM Cugliandolo, JG Beton, CEM Stevenson, BW Hoogenboom, AD Bates, A Maxwell, SA Harris (2020). "Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and recognition", Accepted in Nat Commun 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact None 
URL https://zenodo.org/record/4105979
 
Title agnesnoy/SerraNA: SerraNA v1.0 
Description By Victor Velasco-Berrelleza and Agnes Noy Published at: V Velasco-Berrelleza, M Burmann, JW Shepherd, MC Leake, R Golestanian, A Noy (2020). "SerraNA: a program to determine nucleic acids elasticity from simulation data" Phys Chem Chem Phys, 22, 19254-19266 https://doi.org/10.1039/D0CP02713H 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact None 
URL https://zenodo.org/record/4105986
 
Title agnesnoy/WrLINE: WrLINEv1.0 
Description By Thana Sutthibutpong and Agnes Noy Published at: Sutthibutpong T, Harris SA, Noy A* (2015). "Comparison of molecular contours for measuring writhe in atomistic supercoiled DNA" J Chem Theor Comput, 11, 2768. DOI:10.1021/acs.jctc.5b00035 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact None 
URL https://zenodo.org/record/4106245
 
Description Catalysis Hub 
Organisation Research Complex at Harwell
Department UK Catalysis Hub
Country United Kingdom 
Sector Public 
PI Contribution Modelling and simulation of enzyme mechanisms for applications in biocatalysts via the Catalysis Hub
Collaborator Contribution Modelling and simulation of enzyme mechanisms for applications in biocatalysts via the Catalysis Hub and training of Hub PDRAs.
Impact Catalysis is a core area of contemporary science posing major fundamental and conceptual challenges, while being at the heart of the chemical industry - an immensely successful and important part of the overall UK economy (generating in excess of £50 billion per annum). UK catalytic science currently has a strong presence, but there is intense competition in both academic and industrial sectors, and a need for UK industrial activity to shift towards new innovative areas posing major challenges for the future. In light of these challenges the UK Catalysis Hub endeavours to become a leading institution, both nationally and internationally, in the field and acts to coordinate, promote and advance the UK catalysis research portfolio. With a strong emphasis on effective use of the world-leading facilities on the RAL campus. Structure The project has four mature themes and a fifth theme starting in 2015 , each with a lead investigator as PI - Catalysis by Design (Catlow); Energy (Hardacre); Environment (Hutchings); Chemical Transformations (Davidson) and the new Biocatalysis and Biotransformations (Nick Turner Manchester) - with the design theme based in the Harwell hub. Each theme is supported by £3 - 3.5M EPSRC funding over 5 years and within each theme there are typically six to eight sub-projects funded initially for 2 years, involving collaborative teams working at a variety of sites throughout the UK. Professor Hutchings acts as director of the whole national programme for the first three year period and chairs the management group, which is supported by a steering group and an industrial advisory panel. We note that engagement with industry is one of the key aims of the catalysis hub project. As well as hosting the design theme, the centre within the Research Complex at Harwell (RCaH) will coordinate the programme, be a base for national and international visitors and provide both training and outreach activities.
Start Year 2015
 
Description Collaboration with Beata Vertessy 
Organisation Budapest University of Technology and Economics
Department Department of Biotechnology and Food Sciences
Country Hungary 
Sector Academic/University 
PI Contribution We initiated a collaborative project to studey the role of conserved arginine residues in the dUTPase enzyme. We first performed a PDB-side structural analysis to compare arginine residues in NTP cleaving enzymes. Subsequently, we carried out QM/MM and MD calculations to establish the function of the key arginine finger residue in dUTPases.
Collaborator Contribution In this collaboration the experimental group led by Beata Vertessy performed X-Ray crystallography experiments togeter with biochemical experiments to use this in our joint project.
Impact Nagy et al, Journal of the American Chemical Society, 2016, DOI: 10.1021/jacs.6b09012 Multidisciplinary collaboration with experimental X-Ray crystallography and biochemistry group and our theoretical and computational biophysical chemistry group.
Start Year 2014
 
Description Collaboration with Bristol university on predicting drug-target binding kinetics 
Organisation University of Bristol
Department School of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution We contributed our enhanced sampling simulation algorithms including TS-PPTIS. Our approach will be combined with Prof. Mulholland's QM/MM algorithms to accurately predict binding kinetics.
Collaborator Contribution Prof. Mulholland's contributed his QMMM algorithms as well as Waterswap to the combined computational platform.
Impact A combined computational platform to predict binding kinetics and model the transition state ensemble.
Start Year 2015
 
Description Collaboration with CCP-EM/CCP4 for gylcosylated proteins 
Organisation York Structural Biology Laboratory (YSBL)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution I share knowledge about molecular simulations (including visiting York and giving a talk).
Collaborator Contribution They contribute knowlege about glycans and structural biology.
Impact no publications yet
Start Year 2019
 
Description Collaboration with Derick Rousseau 
Organisation Ryerson University
Country Canada 
Sector Academic/University 
PI Contribution Coarse-grained molecular simulation of monoglyceride self-assembly at triglyceride-water and air-water interfaces.
Collaborator Contribution Experimental studies on the molecular templating effect of monoglycerides on triglyceride crystallization at oil-water interfaces
Impact A poster and oral presentation was given at Food Colloids 2016 held at Wageningen university the Netherlands. A manuscript has been submitted and is under review.
Start Year 2016
 
Description Collaboration with Dr. Alice Pyne, University of Sheffield 
Organisation Henry Royce Institute
Department Henry Royce Institute – University of Sheffield Facilities
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual input and expertise, time of PhD student and access to data
Collaborator Contribution Access to the Henry Royce center through a participation scheme with time dedicated from the Research Officer and in kind materials
Impact -Article in Nature Communications, DOI: 10.1038/s41467-021-21243-y -Articles in Media: Daily Express, Daily Mail, Yahoo News and Deccan Herald -Interviews in Media: Alice Pyne at ITV
Start Year 2016
 
Description Collaboration with Dr. Tung Le, JIC, Norwich 
Organisation John Innes Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise and PhD student time to perform MD simulations that support the experiments
Collaborator Contribution They provide the experimental structures
Impact A publication in Cell Reports (2020), DOI: 10.1016/j.celrep.2020.107928
Start Year 2019
 
Description Collaboration with Johnson and Johnson 
Organisation Johnson & Johnson
Department Janssen-Cilag
Country Global 
Sector Private 
PI Contribution We helped J & J implement a computational pipeline for cryptic binding pocket discovery and collaborated on looking for druggable cryptic binding pockets on targets such the IMPase.
Collaborator Contribution Provided interesting drug targets and experimental data, including NMR fragment screening.
Impact Found interesting cryptic pockets in IMPase
Start Year 2020
 
Description Collaboration with Paul Clegg 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution This project was collaborative with UoE who provided experimental expertise to complement computer modelling at HWU.
Collaborator Contribution Provided expertise in soft matter physics, atomic force microscopy, spectroscopy.
Impact We have authored 5 papers (6th in preparation). These are listed under this award.
Start Year 2016
 
Description Collaboration with Prof. Anthony Maxwell, JIC, Norwich and Inspiralis 
Organisation John Innes Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Performed simulations and write a CASE studentship
Collaborator Contribution He put us in contact with the company Inspiralis
Impact CASE studentship: EP/W524657/1
Start Year 2021
 
Description Collaboration with Prof. Fred Antson (York) and Cyril Sanders (Sheffield) 
Organisation University of Sheffield
Department Sheffield Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution Secure a PhD studentship
Collaborator Contribution Share data and expertise
Impact Shared PhD student ship (EP/N509802/1) Manuscript in preparation
Start Year 2017
 
Description Collaboration with Prof. Jose Maria Lluch's group 
Organisation Autonomous University of Barcelona (UAB)
Country Spain 
Sector Academic/University 
PI Contribution We helped to carry out and analyse QM/MM MD simulations using umbrella sampling bias, and calculated the kinetics as well as the free energies of the catalytic reaction to obtain the Arrhenius prefactor.
Collaborator Contribution Patricia Laura, a PhD student was awarded funding to visit my group and work in my lab.
Impact Joint publication by Suardiaz et al, J. Chem. Theor. Comput. 2016, DOI: 10.1021/acs.jctc.5b01236.
Start Year 2015
 
Description Collaboration with Prof. Lynn Zechiedrich, Baylor College of Medicine, and Twister Biotech, USA 
Organisation Baylor College of Medicine
Country United States 
Sector Hospitals 
PI Contribution Leading the project and providing the PhD students for doing simulations and experiments
Collaborator Contribution Synthesis of DNA minicircles
Impact As a result of this collaboration we have DNA minicircles for performing experiments
Start Year 2018
 
Description Collaboration with Prof. Lynn Zechiedrich, Baylor College of Medicine, and Twister Biotech, USA 
Organisation Twister Biotech
Country United States 
Sector Private 
PI Contribution Leading the project and providing the PhD students for doing simulations and experiments
Collaborator Contribution Synthesis of DNA minicircles
Impact As a result of this collaboration we have DNA minicircles for performing experiments
Start Year 2018
 
Description Collaboration with Prof. Phil Holliger, MRC-LMB, Cambridge 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise and time to perform MD simulations that support the experiments
Collaborator Contribution Intellectual contribution and expertise on evolutionary molecular biology
Impact Publication in eLIFE, 2022 with more than 10 citations in a year, DOI: 10.7554/eLife.75186
Start Year 2021
 
Description Collaboration with SANOFI and Evotec on the allosteric regulation of receptor Tyrosine kinases. 
Organisation Evotec
Country Germany 
Sector Private 
PI Contribution In this successful partnership, we helped designing a new class of allosteric anticancer drugs by using our novel computational algorithms to sample rare events and predict binding kinetics.
Collaborator Contribution The partners contributed to the success of the research by performing large scale ligand screening ad providing high resolution crystallographic structures and biophysical data on the ligand-target complex.
Impact A novel allosteric inhibitor is in re-clinical development for cancer.
Start Year 2015
 
Description Collaboration with SANOFI and Evotec on the allosteric regulation of receptor Tyrosine kinases. 
Organisation Sanofi
Department Aventis
Country France 
Sector Private 
PI Contribution In this successful partnership, we helped designing a new class of allosteric anticancer drugs by using our novel computational algorithms to sample rare events and predict binding kinetics.
Collaborator Contribution The partners contributed to the success of the research by performing large scale ligand screening ad providing high resolution crystallographic structures and biophysical data on the ligand-target complex.
Impact A novel allosteric inhibitor is in re-clinical development for cancer.
Start Year 2015
 
Description Collaboration with UCB pharma on cryptic sites 
Organisation UCB Pharma
Country United Kingdom 
Sector Private 
PI Contribution We contributed our new computational methods to find cryptic binding sites.
Collaborator Contribution Experimental validation, including crystal structures, surface plasmon resonance, new compounds.
Impact Helped develop new drug candidates.
Start Year 2018
 
Description Developing new computational approaches to inhibit "undruggable" targets. 
Organisation UCB Pharma
Country United Kingdom 
Sector Private 
PI Contribution We shared with UCB early versions of a computational platform we are developing to target allosteric sites on otherwise "undruggable" targets, i.e. pharmaceutical targets that are difficult to target with traditional drug design approaches based on substrate competitive ligands.
Collaborator Contribution UCB contributed to the project with high quality structural and biological data and is hiring a dedicated PDRA to work on the collaboration for 3 years.
Impact The new tools have been used to design novel drugs.
Start Year 2016
 
Description Evotec AI 
Organisation Evotec (UK) Ltd
Country United Kingdom 
Sector Private 
PI Contribution Studentship aimed at researching the use of MD in Artificial Intelligence.
Collaborator Contribution None yet.
Impact N/A yet.
Start Year 2018
 
Description Industrial collaboration with EVOTEC 
Organisation Evotec
Country Germany 
Sector Private 
PI Contribution We helped EVOTEC to rationalize the binding mode of a novel allosteric modulator of FGFR. By using our novel "SWISH" Hamiltonian Replica exchange algorithm, we predicted a previously unknown binding cavity in the D3 domain of FGFR3c, which was then validated by NMR spectroscopy.
Collaborator Contribution Evotec provided a plethora of unpublished experimental data on the binding mode and on the biological effect of the new tool compound in cells.
Impact The collaboration is multi-disciplinary involving Computational Chemistry, Chemical Biology, Structural Biology, Cellular Biology and Drug Discovery. A new manuscript is in preparation and will soon be submitted to a very prominent and high-impact journal. The PI (FLG) has been invited to a number of high-profile national international (ACS-meeting) conferences to discuss the results.
Start Year 2016
 
Description MARISURF 
Organisation Marlow Foods
Country United Kingdom 
Sector Private 
PI Contribution MARISURF is a 4.8Meuro H2020 project coordinated by HWU to identify, isolate and purify biosurfactants from marine bacteria. The production will then be scaled up to pilot scale and the surfactants tested by industrial end-users from various industry sectors including food, cosmetic and biomedical sectors. My research group is responsible for overall coordination of the project, and specifically for the screening of functional properties of the surfactants to ensure suitability in industrial applications.
Collaborator Contribution Marlow Foods are a partner in MARISURF an EUH2020 project coordinated by HWU. They will test marine bacteria-derived surfactants in their Quorn food applications.
Impact The collaboration is multi-disciplinary and involves the following scientific disciplines, Microbiology Chemistry Biochemistry Molecular Biology Process Engineering
Start Year 2015
 
Description Modelling of enzyme catalysed reaction mechanisms relevant to pharmaceutical development 
Organisation Pfizer Ltd
Country United Kingdom 
Sector Private 
PI Contribution Confidential
Collaborator Contribution Confidential
Impact Confidential
Start Year 2011
 
Description Organic synthesis of alternative gelator molecules 
Organisation Heriot-Watt University
Department Department of Mathematics
Country United Kingdom 
Sector Academic/University 
PI Contribution Shared information on olegelation. Invited collaborator to project meetings. Eventual joint publications.
Collaborator Contribution The partner will synthesize a range of alternative olegelator molecules that are derivatives of gamma oryzanol that either have the ferullic acid side chain substituted for another group, or have a hydroxyl group substituted. The hydroxyl group is believed to be important in dimerization of the sterols prior to their subsequent self-association into tubules, and also stabilizes the tubules through cooperative H-bonding. The ferrulic acid group is believed to allow inter-tubule interaction (it sticks out from the surface of the tubule) via pi-pi stacking interactions, thus leading to gel formation. By creating and testing oleogelators where one or both of these groups has been substituted will allow us to understand the role they play in the self-association and gelation process.
Impact Too early in project/collaboration.
Start Year 2017
 
Description Participation of European Topology interdisciplinary Initiative (Eutopia) network 
Organisation European Cooperation in Science and Technology (COST)
Department COST Action
Country Belgium 
Sector Public 
PI Contribution I gave a talk and exchanged views and knowledge with scientific colleagues
Collaborator Contribution The network invited me to give a talk
Impact I gave a talk to the 2nd annual meeting of the network It is a multidisciplinary network from mathematics to biology, physics and chemistry.
Start Year 2019
 
Description Vertex - CFTR 
Organisation Vertex Pharmaceuticals
Country United States 
Sector Private 
PI Contribution This is a studentship that will commence in 2019.
Collaborator Contribution None yet.,
Impact N/A.
Start Year 2019
 
Description collaboration with Novartis 
Organisation Novartis
Department Drug Discovery & Development
Country United States 
Sector Private 
PI Contribution We have shared data and software/home-made code to derive kinetic rates from umbrella sampling simulations. We also developed methods to be used for calculating residence times frlom atomistic simulations.
Collaborator Contribution Shared data with us of atomistic simulations for drug molecules crossing the membrane.
Impact We have joint publications.
Start Year 2018
 
Description collaboration with Walter Kolch 
Organisation University College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution Computational MD simulations to reveal structure and dynamics of RAF kinases.
Collaborator Contribution Prof. Kolch's group carried out in vitro and in cell biochemical experiments to reveal RAF kinase activity and validate key mutations suggested by computational results.
Impact Jambrina et al, Angewandte Chemie, 2016, DOI: 10.1002/anie.201509272 Sanchez-Sanz et al, PLOS Computational Biology, 2016, DOI: 10.1371/journal.pcbi.1005051 Interdisciplinary research with essential biochemical and biological experiments from the Kolch group (Systems Biology Ireland) and computational work from our group.
Start Year 2012
 
Description water network analysis 
Organisation University of Oxford
Department Department of Biochemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Training and insights related to our methods.
Collaborator Contribution Partners provided the data and and associated collaborators for us to use in our analysis.
Impact Paper reporting collaboration results published,
Start Year 2016
 
Title APPARATUS FOR AND METHOD OF PROCESSING BIOLOGICAL SAMPLES 
Description The present invention provides systems, devices, apparatuses and methods for automated bioprocessing. Examples of protocols and bioprocessing procedures suitable for the present invention include but are not limited to: immunoprecipitation, chromatin immunoprecipitation, recombinant protein isolation, nucleic acid separation and isolation, protein labeling, separation and isolation, cell separation and isolation, food safety analysis and automatic bead based separation. In some embodiments, the invention provides automated systems, automated devices, automated cartridges and automated methods of western blot processing. Other embodiments include automated systems, automated devices, automated cartridges and automated methods for separation, preparation and purification of nucleic acids, such as DNA or RNA or fragments thereof, including plasmid DNA, genomic DNA, bacterial DNA, viral DNA and any other DNA, and for automated systems, automated devices, automated cartridges and automated methods for processing, separation and purification of proteins, peptides and the like. 
IP Reference US2018111121 
Protection Patent application published
Year Protection Granted 2018
Licensed Yes
Impact the patent has been instrumental for the incorporation of the spin out company Vitamica Ltd
 
Title Confidential 
Description Confidential 
IP Reference Confidential 
Protection Patent / Patent application
Year Protection Granted 2024
Licensed Commercial In Confidence
Impact Confidential
 
Title METHOD AND APPARATUS FOR BACTERIAL ANALYSIS 
Description An apparatus (10) comprising: a light source (12); to cast light toward a substrate (20) defining a bacteria binding volume to create an evanescent field (22), the bacteria binding volume being within the evanescent field; a detector (32, 34) arranged to receive light from the bacteria binding volume and output data (36, 37); and a processor (38) arranged to determine vibration of bacteria (26) within the bacteria binding volume in three-dimensions from the data. 
IP Reference WO2019025771 
Protection Patent application published
Year Protection Granted 2019
Licensed Yes
Impact The patent has being instrumental for the incorporation of the spin out company Vitamica Ltd.
 
Title METHOD FOR DETECTION OF INTESTINAL, AND BLOOD-BRAIN BARRIER PERMEABILITY AND TESTING MATERIALS THERETO 
Description METHOD FOR DETECTION OF INTESTINAL, AND BLOOD-BRAIN BARRIER PERMEABILITY AND TESTING MATERIALS THERETO Methods, assays, and apparatus are disclosed for testing of antigens associated with intestinal and/or blood-brain barrier permeability. For example, blood, saliva or other bodily fluid can be tested for binding (1) to a bacterial toxin (preferably a lipopolysaccharide), and (2) binding to tissue antigens selected from at least one of (a) a gut-related antigen and (b) a blood brain barrier-related antigen. Analysis of test results can be used to assist in detecting and diagnosing diseases associated with leaky gut syndrome (whether due to paracellular or transcellular pathways, and whether due to bacterial toxins or some other cause) and/or to diseases associated with excessive blood brain barrier permeability, which are contemplated herein to include both neuroinflammation and/or neuroautoimmunity conditions, and especially amyotrophic lateral sclerosis, Parkinsons disease, multiple sclerosis, Alzheimer's, or peripheral neuropathy, and major depression. 
IP Reference AU2016259430 
Protection Patent application published
Year Protection Granted 2016
Licensed Yes
Impact the patent has been instrumental for the incorporation of the spin out company Vitamica Ltd
 
Title BioSimSpace 
Description BioSimSpace is an interoperable Python framework for biomolecular simulation. It is the Flagship Software Development Project of CCP-BioSim. With it you can: -Write robust and portable biomolecular workflow components that work on different hardware, with different software packages, and that can be run in different ways, e.g. command-line, Jupyter. -Interact with running molecular simulation processes in real-time. BioSimSpace is a new software framework to create an interoperability layer around the many software packages that are already embedded within the biosimulation community. BioSimSpace will enable rapid development of workflows between these software packages that can then be used in conjunction with existing workflow software such as Knime, Pipeline Pilot, ExTASY etc. See: https://biosimspace.org 
Type Of Technology Software 
Year Produced 2018 
Open Source License? Yes  
Impact BioSimSpace has been used in several CCP-BioSim training workshops, and is now being applied in collaboration with industrialists and experimentalists. 
URL http://www.ccpbiosim.ac.uk
 
Title CCP-BioSim software for biomolecular simulation 
Description BioSimSpace A new software framework to create an interoperability layer around the many software packages that are already embedded within the biosimulation community. BioSimSpace will enable rapid development of workflows between these software packages that can then be used in conjunction with existing workflow software such as Knime, Pipeline Pilot, ExTASY etc. This project is currently in an early phase of development, more information can be found here. FESetup FESetup is a tool to automate the setup of (relative) alchemical free energy simulations like thermodynamic integration (TI) and free energy perturbation (FEP) as well as post-processing methods like MM-PBSA and LIE. FESetup can also be used for general simulation setup ("equilibration") through an abstract MD engine. The latest releases are available from the project web page. Other Software: ProtoMS - a complete protein Monte Carlo free energy simulation package. Sire - a complete python/C++ molecular simulation framework, particularly focussed around Monte Carlo, QM/MM and free energy methods. PCAZIP - a toolkit for compression and analysis of molecular dynamics trajectories. COCO - a tool to enrich an ensemble of structures, obtained e.g. from NMR. Handy Routines for Ptraj/Cpptraj - additional analysis methods for ptraj and cpptraj. 
Type Of Technology Software 
Year Produced 2016 
Open Source License? Yes  
Impact BioSimSpace A new software framework to create an interoperability layer around the many software packages that are already embedded within the biosimulation community. BioSimSpace will enable rapid development of workflows between these software packages that can then be used in conjunction with existing workflow software such as Knime, Pipeline Pilot, ExTASY etc. This project is currently in an early phase of development, more information can be found here. FESetup FESetup is a tool to automate the setup of (relative) alchemical free energy simulations like thermodynamic integration (TI) and free energy perturbation (FEP) as well as post-processing methods like MM-PBSA and LIE. FESetup can also be used for general simulation setup ("equilibration") through an abstract MD engine. The latest releases are available from the project web page. Other Software: ProtoMS - a complete protein Monte Carlo free energy simulation package. Sire - a complete python/C++ molecular simulation framework, particularly focussed around Monte Carlo, QM/MM and free energy methods. PCAZIP - a toolkit for compression and analysis of molecular dynamics trajectories. COCO - a tool to enrich an ensemble of structures, obtained e.g. from NMR. Handy Routines for Ptraj/Cpptraj - additional analysis methods for ptraj and cpptraj. 
URL http://www.ccpbiosim.ac.uk
 
Title CCPBioSim Online Self-guided Training 
Description Tutorials (many based on Jupyter Notebooks) are deployed through containers and accessed through the CCPBioSim website. They cover a range of topics similar to our training events. 
Type Of Technology Webtool/Application 
Year Produced 2019 
Impact The online nature of these tutorials has allowed us to expand our reach and help more people gain computational biology skills. 
URL http://www.ccpbiosim.ac.uk/training
 
Title CCPBioSim Web Portal 
Description A new web portal was launched to replace the old CCPBioSim drupal based website. The new web portal was designed to bring the CCPBioSim web presence in-line with that of HECBioSim. The new portal focuses on providing a collaborative environment where members of the consortium management can create material together that has a consistent and quality look and feel to users, this includes event related materials for conferences and workshops. 
Type Of Technology Webtool/Application 
Year Produced 2016 
Impact Since the launch of the new portal in February 2016, the portal has had around 50,000 hits by 17,847 unique IP addresses indicating that the website has a quite broad reach within the UK bio-simulation community. 
URL http://www.ccpbiosim.ac.uk
 
Title Containerised cloud training platform 
Description The cloud training platform was developed to offer both the HEC and the CCP consortia a new flexible approach to training in the latest and next generation scientific techniques, methodologies and tools. This platform consists of a catalogue of docker containers containing software compiled by our experts, a catalogue of code repositories containing training courses writen by our experts in the JupyterHub/Lab format. This is all brought together in the cloud via kubernetes and results in a platform that researchers and students in our community can simply navigate to our training section on our website and click the course they want to do and the platform will provision a virtual environment with all software and course material ready for them. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2019 
Impact We have been using this platform to deliver consortia training events in the programme. This has allowed us to deliver thousands of training hours (3,051) across all our courses online and to deliver thousands more (2,510) in instructor led sessions. When the Covid-19 pandemic hit, this infrastructure allowed us to move immediately from events at physical locations to fully online backed by zoom lectures. We even scaled up to having over 400 delegates register with around 200 attending a given session where as we only used to allow around 50 to register and 30 to attend a given session previously with in person classes. 
URL http://www.ccpbiosim.ac.uk/training
 
Title FESetup 
Description FESetup FESetup is a tool to automate the setup of (relative) alchemical free energy simulations like thermodynamic integration (TI) and free energy perturbation (FEP) as well as post-processing methods like MM-PBSA and LIE. FESetup can also be used for general simulation setup ("equilibration") through an abstract MD engine. The latest releases are available from the project web page. 
Type Of Technology Software 
Year Produced 2017 
Impact FESetup FESetup is a tool to automate the setup of (relative) alchemical free energy simulations like thermodynamic integration (TI) and free energy perturbation (FEP) as well as post-processing methods like MM-PBSA and LIE. FESetup can also be used for general simulation setup ("equilibration") through an abstract MD engine. The latest releases are available from the project web page. 
 
Title Longbow v1.5 
Description Longbow is a piece of software that acts as a job proxying tool for biomolecular simulations, Longbow reproduces the native look and feel of using popular molecular dynamics packages (AMBER, CHARMM, GROMACS, LAMMPS and NAMD), with the difference that when those packages are used through Longbow simulations can be run on High Performance Computing (HPC) resources such as ARCHER. Longbow handles jobs setup in terms of creating job submission scripts, automatically stages input files, launches and monitors jobs and stages back simulation results. The option is also there to persistently monitor and stage (realtime local syncing with remote simulation files) simulation files at a specified time interval. This is designed to have the jobs running on the HPC remote resource appear to the user as if the simulation has run on their local computer/cluster. Users do not have to concern themselves with writing submission files, nor do they have to worry about staging. Longbow provides a convenient interface for generating large ensembles of simulation jobs which in effect extends the packages it supports. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Longbow has now been downloaded 1,523 times from the HECBioSim website and tens of thousands of times from the pypi directory (July 2017). It has a wide reaching user-base across the world, some of those users being at 26 UK institutions actively downloading new versions as they are released. This version was a major new release which focused on addressing a number of architectural problems, this required major refactoring of the code base. This version fixed a number of community reported bugs and added user requested new functionality. Support for the latest python 3 version was added and the API restructured to simplify uptake in other projects. 
URL https://github.com/HECBioSim/Longbow/releases/tag/v1.5.0
 
Title Plug-in and scripts for enhanced-sampling molecular simulations. 
Description We developed a new interoperable plug-in compatible with PLUMED and many widely-used MD codes (such as GROMACS) to run our TS-PPTIS approach for binding kinetics. The tool can be used to predict ligand and folding binding kinetics. 
Type Of Technology Software 
Year Produced 2016 
Open Source License? Yes  
Impact The tool is able to accurately predict the binding kinetics of drugs to their biological targets, paving the avenue to the rational design of new molecules with fine-tuned biomedical effects. 
 
Title ProtoCaller 
Description Software to automate the setup of free energy calculations 
Type Of Technology Software 
Year Produced 2020 
Open Source License? Yes  
Impact non yet 
URL https://protocaller.readthedocs.io/en/latest/index.html
 
Title ProtoMS 3.2 
Description This software allows for the calculation of protein-ligand binding free energies. This most recent version incorporates our latest work on grand canonical Monte Carlo. 
Type Of Technology Software 
Year Produced 2015 
Open Source License? Yes  
Impact This software is being adopted by other academics and some industrial partners are also using it. 
URL http://www.essexgroup.soton.ac.uk/ProtoMS/
 
Title ProtoMS 3.3 
Description This software allows the user to perform protein-ligand binding free energy calculations using advanced Monte Carlo methods, including grand canonical Monte Carlo. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact This software is currently being deployed to industrial collaborators. Its impact in this context will be assessed once these deployments are complete. 
URL http://www.essexgroup.soton.ac.uk/ProtoMS/index.html
 
Title Sire 2014.4 
Description 2014.4 release of Sire. Molecular simulation framework. Main enhancement was the inclusion of new code that accelerated key routines. 
Type Of Technology Software 
Year Produced 2014 
Open Source License? Yes  
Impact Sire is now in use in a number of pharmaceutical companies for applications in drug design and development 
URL http://www.siremol.org/Sire/Home.html
 
Title Software - Crossflow 
Description Crossflow is a Python framework for writing computational workflows for execution on distributed computing facilities. 
Type Of Technology Software 
Year Produced 2020 
Open Source License? Yes  
Impact The software is currently being evaluated by UCB for use in their drug discovery activities 
URL http://bitbucket.org/claughton/crossflow.git
 
Title WaterDock 
Description A software to predict the location of water molecules in proteins. 
Type Of Technology Software 
Year Produced 2016 
Open Source License? Yes  
Impact N/A 
URL https://github.com/bigginlab/WaterDock-2.0
 
Title agnesnoy/SerraLINE: SerraLINE v1.0 
Description Version utilized in the paper: ALB Pyne, A Noy, K Main, V Velasco-Berrelleza, MM Piperakis, LA Mitchenall, FM Cugliandolo, JG Beton, CEM Stevenson, BW Hoogenboom, AD Bates, A Maxwell, SA Harris (2020). "Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and recognition", Accepted in Nat Commun 
Type Of Technology Software 
Year Produced 2020 
Open Source License? Yes  
Impact Publication 
URL https://zenodo.org/record/4105979
 
Title agnesnoy/SerraNA: SerraNA v1.0 
Description By Victor Velasco-Berrelleza and Agnes Noy Published at: V Velasco-Berrelleza, M Burmann, JW Shepherd, MC Leake, R Golestanian, A Noy (2020). "SerraNA: a program to determine nucleic acids elasticity from simulation data" Phys Chem Chem Phys, 22, 19254-19266 https://doi.org/10.1039/D0CP02713H 
Type Of Technology Software 
Year Produced 2020 
Impact Publication and use on subsequent research 
URL https://zenodo.org/record/4105987
 
Title agnesnoy/WrLINE: WrLINEv1.0 
Description By Thana Sutthibutpong and Agnes Noy Published at: Sutthibutpong T, Harris SA, Noy A* (2015). "Comparison of molecular contours for measuring writhe in atomistic supercoiled DNA" J Chem Theor Comput, 11, 2768. DOI:10.1021/acs.jctc.5b00035 
Type Of Technology Software 
Year Produced 2020 
Impact Used in several publications and in current research 
URL https://zenodo.org/record/4106245
 
Company Name Vitamica 
Description Vitamica develops a testing device that analyses samples to detect effective antibodies. 
Year Established 2018 
Impact The company is working on the development of a rapid AMR diagnostic device that could be used in healthcare, veterinary and pharma sectors.
Website http://www.vitamica.co.uk
 
Description 19th International Union of Pure and Applied Biophysics (IUPAB) and 11th European Biophysical Societies Association (EBSA) Congress in Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Agnes Noy succeed to be selected for giving a talk on the most relevant international conference of the year on Biophysics.
Year(s) Of Engagement Activity 2017
URL http://www.iupab2017.org/home
 
Description 6th Molecular Microbiology Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact I attended this conference and I gave a talk with the purpose of engaging with microbiologists on multidisciplinary exchange of knowledge
Year(s) Of Engagement Activity 2019
URL https://conferences.ncl.ac.uk/molmicro2019/
 
Description Advanced technology to support research, innovation and economic growth in the UK 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Reform hosted a policy roundtable on the opportunities for advanced technology in the UK in May 2019, with the kind support of Hewlett Packard Enterprise. The session was introduced by Chris Skidmore MP, then Minister of State for Universities, Science, Research and Innovation, and Professor Mark Parsons, Director at the Edinburgh Parallel Computing Centre.

The Minister stressed the importance of international collaboration in R&D, reaffirming the UK's ambition to strengthen and enrich existing
partnerships, as well as to develop new global partnerships - as outlined in the then recently announced International Research & Innovation
Strategy. The discussion also focused on the opportunities the upcoming Comprehensive Spending Review would offer to the science, research and innovation sectors, and on the need to build a strong case for. investment in emerging technologies - including quantum technology, performance computing (HPC) and robotics.

During this meeting it was highlighted that High-performance computing is considered a game-changing technology, which will be fundamental
to the UK's ability to maintain its global competitiveness in the science, research and innovation sectors.
Year(s) Of Engagement Activity 2019
URL https://reform.uk/research/advanced-technology-support-research-innovation-and-economic-growth-uk
 
Description Alchemistry in Boston 2018 - Bluck and Biggin 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A poster was presented on free energy calculations and received useful feedback.
Year(s) Of Engagement Activity 2018
 
Description Article in IFLScience 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article at the online magazine IFLScience focused in dessmination of scientific news. After 24 hours it had more than 1000 shares
Year(s) Of Engagement Activity 2021
URL https://www.iflscience.com/editors-blog/highestresolution-images-of-dna-ever-reveal-how-it-dances/
 
Description Article in Phys.org 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Article at the Phys.org magazine
Year(s) Of Engagement Activity 2021
URL https://phys.org/news/2021-02-visualization-dna.html
 
Description Article in the Daily Express 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Article in the Daily Express on the article in Nature Communications 2021
Year(s) Of Engagement Activity 2021
URL https://www.express.co.uk/news/science/1398473/dancing-dna-highest-resolution-pictures-dna-molecules...
 
Description Article in the Daily Mail 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Article in the press on the Nature Communications 2021
Year(s) Of Engagement Activity 2021
URL https://www.dailymail.co.uk/sciencetech/article-9265951/Scientists-capture-highest-resolution-images...
 
Description Banff International Research Station for Mathematical Innovation and Discovery: "The Topology of Nucleic Acids" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited talk that has been made accessible online
Year(s) Of Engagement Activity 2019
URL https://www.birs.ca/events/2019/5-day-workshops/19w5226
 
Description Biocomputation workshop sponsored by the Physics-of-Life network in Durham 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Agnes Noy participated on the organization of this event in designing the program and selecting the speakers. The event was around the future and scope of biocomputation and how the ideas were articulated for future grants. A grant application was produced as a result of that workshop
Year(s) Of Engagement Activity 2017
URL http://www.physicsoflife.org.uk/biocomputation.html
 
Description Biomolecular Simulations Presentation, DLS, November 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Sarah Fegan gave a presentation on "Biomolecular Simulations" at the Simulations for Experimentalists and Industrialists training course at Diamond Light Source, 7 November 2018. This led to discussions about future research activities.
Year(s) Of Engagement Activity 2018
 
Description Blog and twitter account 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Blog about the scientific research done in my group together with a twiter account @ANoyLab
Year(s) Of Engagement Activity 2019
URL http://agnesnoylab.wordpress.com/
 
Description Bristol Chemshell training Feb 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Tom Keal and You Lu gave a 2-day training course in the use of ChemShell for materials and biomolecular modelling to a group of 15 researchers at the University of Bristol
Year(s) Of Engagement Activity 2019
 
Description CCP5 Summer School, Advanced Lectures in Biomolecular Simulation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dr Richard Henchman and Dr Syma Khalid delivered lectures and workshops over three days on how to use simulations study biomolecular systems (setting them up, running them, analysing them). This drew on material given at other CCP-Biosim training events. About 25 student attended from the UK and Europe. The module delivered is one of three given in parallel. Preceding this was the five-day core part of the Summer School.
Year(s) Of Engagement Activity 2015
URL http://www.ccp5.ac.uk/events/summer_school_2015/
 
Description CCPBioSim 2019 annual conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact In total, 103 academics, (PhD) students and researchers in industry attended the CCPBioSim conference. The talks and posters presented at the meeting sparked wide-ranging scientific discussions. The feedback was overwhelmingly positive.
(Co-chairs: Marc van der Kamp and Adrian Mulholland)
Year(s) Of Engagement Activity 2019
URL http://www.ccpbiosim.ac.uk/events/past-conferences/eventdetail/119/-/7th-annual-ccpbiosim-conference...
 
Description CCPBioSim Biomolecular QM/MM Modelling with ChemShell workshop, June 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact CCPBioSim held a training day on combined quantum mechanical/molecular mechanical (QM/MM) modelling of biomolecular systems at the University of St Andrews on 14 June 2018 as part of the ScotCHEM 2018 conference. In the morning session we discussed the principles of QM/MM modelling and introduced the ChemShell software package. ChemShell is a scriptable computational chemistry environment which provides a flexible way to link QM and MM codes together to perform QM/MM calculations. There was then an opportunity to learn the basics of ChemShell in the first practical. In the second lecture we described in more depth how QM/MM biomolecular calculations are set up and performed, using a cytochrome P450 system as a case study. The second practical explored modelling of enzymatic reactions with ChemShell on STFC's SCARF cluster.
Year(s) Of Engagement Activity 2018
URL https://www.scotchem.ac.uk/st-andrews-2018/
 
Description CCPBioSim Biomolecular QM/MM Modelling with ChemShell workshop, May 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact CCPBioSim held a training day on combined quantum mechanical/molecular mechanical (QM/MM) modelling of biomolecular systems at STFC Daresbury Laboratory on the 9th May 2017.In the morning session we discussed the principles of QM/MM modelling and introduced the ChemShell software package. ChemShell is a scriptable computational chemistry environment which provides a flexible way to link QM and MM codes together to perform QM/MM calculations. There was then an opportunity to learn the basics of ChemShell in the first practical. In the second lecture we described in more depth how QM/MM biomolecular calculations are set up and performed, using a cytochrome P450 system as a case study. The second practical explored modelling of enzymatic reactions with ChemShell on the Hartree Centre systems. In the final lecture we showcased recent ChemShell developments.
Year(s) Of Engagement Activity 2017
URL http://www.ccpbiosim.ac.uk/events/workshop-course-material/eventdetail/95/-/qm-mm-modelling-of-biomo...
 
Description CCPBioSim Training Week 2018 - QM/MM enzyme reaction modelling 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact During the CCPBioSim training week in 2018, I led a training workshop to introduce non-specialists to the use of combined quantum mechanics/molecular mechanics (QM/MM) methods for modelling enzyme-catalysed reaction mechanisms. I developed new, open-source course material for this, available online. 25 people attended, and evaluated very positively (>60% would strongly recommend the workshop to colleagues, 100% found the workshop (very) useful). Excellent discussion afterwards with several attendees.
Year(s) Of Engagement Activity 2018
URL https://ccpbiosim.github.io/qmmm_workshop/
 
Description CCPBioSim training week, October 2020 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact The CCPBioSim Training Week was held online 2-9 October 2020, organised by Sarah Fegan, Sarah Harris and Charlie Laughton. The topics covered ranged from the basics of biomolecular simulation to QM/MM calculations and there were talks from CCP5 and CCP-EM. There were 17 sessions including three plenary research seminars by Syma Khalid (University of Southampton), Prem Chapagain (Florida International University, USA) and Viv Kendon (Durham University; Chair of CCP-QC). CoSeC representatives James Gebbie, Alin Elena, Michael Seaton and Tom Burnley all gave presentations at the event.
Year(s) Of Engagement Activity 2020
URL https://www.ccpbiosim.ac.uk/events/workshop-course-material/eventdetail/127/-/training-week-2020
 
Description CECAM workshop "Computational biophysics on your desktop: is that possible?" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invitation of PI grant, Agnes Noy, to give a talk on a CECAM workshop which is a series of scientific conferences
Year(s) Of Engagement Activity 2018
URL https://www.cecam.org/workshop-1534.html
 
Description ChemShell training workshop at PRACE Autumn School 2021: Fundamentals of Biomolecular Simulations and Virtual Drug Development 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A ChemShell biomolecular QM/MM training day was held online as part of the PRACE Autumn School 2021: Fundamentals of Biomolecular Simulations and Virtual Drug Development (20-24 Sep 2021), featuring an introduction to the DL_Software suite by Ilian Todorov, and talks and demonstrations of the ChemShell QM/MM package by Tom Keal, Kakali Sen and You Lu.
Year(s) Of Engagement Activity 2021
URL https://events.prace-ri.eu/event/1222/
 
Description ChemShell training workshop at the CCPBioSim training week, September 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact As part of the CCPBioSim training week 2021, a training session on ChemShell for biomolecular QM/MM calculations was held, with talks and demonstrations from Tom Keal, Kakali Sen, You Lu and Sarah Fegan of STFC.
Year(s) Of Engagement Activity 2021
URL https://www.ccpbiosim.ac.uk/events/workshop-course-material/eventdetail/135/-/ccpbiosim-training-wee...
 
Description Conference paper at Physics in Food manufacturing event, Chipping Campden, January 2019. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Workshop organised by the Institute of Physics food group. Allowed networking with physicists/physical chemists with similar intersts in food science.
Year(s) Of Engagement Activity 2019
 
Description Conference paper on Food Oleogels at EFFost conference November 2018 in Nantes France 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussion were held with industrial (and academic) scientists who were interested in the finding of the work.The computational approaches used were of particular interests to academics and this has fostered new interactions with potential academic collaborators.
Year(s) Of Engagement Activity 2018
 
Description EUTOPIA-2: 2 nd meeting of the European Topology interdisciplinary Initiative 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited talk and enroll at this EU-funded COST network
Year(s) Of Engagement Activity 2019
URL https://eutopiaam2019.wordpress.com
 
Description HECBioSim: tools to simplify running and analysing large-scale MD simulations on HPC resources 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact This workshop was to introduce members of the bio-simulation community to tools that simplify the process of running and analysing MD simulations on a large scale. Users were introduced to consortia developed tools (Longbow pyPcazip and pyPcazipgui), users attempted hands on demonstrations of how to use such software and how to introduce them into their own workflows. Users had access to the national super computing service ARCHER for the duration of this workshop, so they had hands on experience with such resources for the first time in some cases.

This workshop provided users direct exposure to the developers of the tools, which helped to open dialogue between users and developers and bring more ideas for new features.
Year(s) Of Engagement Activity 2015
URL http://www.ccpbiosim.ac.uk/hecbio-goinglarge
 
Description Headstart program at the University of York 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Supporters
Results and Impact Guest lecture "Introduction to Biophysics" to A-level physics students within the Work Experience Week and Headstart programs
Year(s) Of Engagement Activity 2019
URL https://www.york.ac.uk/physics/public-and-schools/events/headstart-2019/
 
Description Industry training workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Training on our software ProtoMS was given to three industrial partners - GSK, AZ and UCB. This involved visits to the industrial sites, presentation of the theory underpinning the work, and the provision of training materials.
Year(s) Of Engagement Activity 2017
 
Description Interview in That's York TV 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Interview for the local TV
Year(s) Of Engagement Activity 2021
URL https://www.facebook.com/ThatsTVYork/
 
Description Istanbul December 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk on free energy.
Year(s) Of Engagement Activity 2018
 
Description Joint CCP-BioSim CCP-EM workshop on Computation for cryo-EM 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The first day of the workshop provided new users of the Fluctuating Finite Element analysis software (developed at Leeds). As this is the first time this software has been used by people outside of the group, we obtained very useful feedback on performance and usability. The software has been adopted by at least one other research team since the event. On the second day, we had the first (to our knowledge) community discussion of the role of computation in cryo-EM from a prestigious range of international speakers. The event was extremely well received, and we are planning a subsequent workshop for 2019.
Year(s) Of Engagement Activity 2017
 
Description London Free Energy Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented a talk on free energy calculations to specialised audience of practitioners including industry attendees.
Year(s) Of Engagement Activity 2017
 
Description Lorentz-Center workshop on DNA Damage and Repair in Leiden, Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Agnes Noy was invited to give a talk and to participate as an expert panel on a dialogue about the subject with numerous questions and long discussions
Year(s) Of Engagement Activity 2017
URL http://www.lorentzcenter.nl/lc/web/2017/932/info.php3?wsid=932&venue=Oort
 
Description Markov modelling and free energy calculation workshop 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact About 50 participants attended the Markov modelling workshop we organised at King's College London, some of which were international scientists from India, Europe or the US. Several participants were from pharmaceutical companies, such as Novartis, GSK, and UCB Pharma. The workshop initiated further collaborations and research visits with both academic groups and pharma companies.
Year(s) Of Engagement Activity 2016
 
Description Multiscale Modelling Conference jointly between CCPBiosim and CCP5 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference of 100 people bringing together experts in the UK, Europe and USA in the area of multiscale modelling in a 2-day conference in Manchester in April 2016. There are about 30 talks and a poster session of about 40 posters. The conference ran previously in January 2014 with a similar size and format.
Year(s) Of Engagement Activity 2014,2016
URL http://www.ccpbiosim.ac.uk/multiscale2016/eventdetail/55/-/2nd-conference-on-multiscale-modelling-of...
 
Description Multiscale modelling presentation, DLS, November 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Tom Keal gave a presentation on "Multiscale modelling of biomolecules and materials" at the Simulations for Experimentalists and Industrialists training course at Diamond Light Source, 7 November 2018
Year(s) Of Engagement Activity 2018
 
Description Pint of Science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Outreach talk for general public about current research in genomes and how affects our lives.
Year(s) Of Engagement Activity 2019
URL https://pintofscience.co.uk/
 
Description Pint of Science talk: Making movies of Bacterial membranes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I gave a talk in a pub to an audience consisting of members of the general public who had bought tickets to the event. The talk explained some of the science behind antimicrobial resistance followed by some details of my own work in terms of 'making movies' of the bacterial membranes so we can understand how they protect bacteria. I talked about how we have to understand the membranes in molecular detail if we are to design new drugs with the ability to permeate across these membranes. Audience members said they had a much better understanding of how they must not abuse antibiotics, after the talk.
Year(s) Of Engagement Activity 2017
URL https://pintofscience.co.uk/event/architecture-with-atoms
 
Description Press release by the University of York 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Press Release on the article on Nature Communications 2021
Year(s) Of Engagement Activity 2021
URL https://www.york.ac.uk/news-and-events/news/2021/research/dna-dancing-video/
 
Description Seeing is Believing: Build a DIY microscope!, Discovery Zone at York Festival of Ideas, UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Family friendly stand at the Science Fair 'Discovery Zone' at York Festival of Ideas, UK
Year(s) Of Engagement Activity 2023
URL https://yorkfestivalofideas.com/2023/calendar/discovery-zone/
 
Description Seminar at University of Leeds 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Seminar on edible oleogels at the University of Leeds to academic staff and students
Year(s) Of Engagement Activity 2017
 
Description Special Seminar on Entropy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Richard Henchman gave a talk about his multiscale cell correlation technique for calculating and analysing entropy from simulation data. The talk was followed by 30 minutes of answering questions from the audience. Abstract: The stability and flexibility of biomolecules are inherent to their properties and function. Entropy is central to both these quantities, first because it is a key component of the free energy, which governs stability, and second because it expresses the probability distribution over all degrees of freedom in a single number. While there are methods to evaluate entropy for specific cases and while there are many partial measures of molecular
flexibility, a general way to evaluate the entropy and full probability distribution is lacking for systems of biomolecular interest. To address this, we present the Multiscale Cell Correlation (MCC) method [1-2] which calculates entropy in a multiscale fashion in terms of cells of correlated units. We apply it to two cases: host-guest complexes [3] and proteins [4]. Binding free energies in the recent SAMP8 Challenge give a 1 kcal mol-1 error, and protein entropies closely match values from normal mode analysis. MCC explains how entropy is distributed over all degrees of freedom in each system. For binding, as expected, the entropy loss of the binding guest is offset by the gain in the released water. In proteins, entropy in the polymer chain is found to be comparable to that within the residues, and the residue entropy is largely independent of solvent exposure due to a compensation between conformational and vibrational entropy.
[1] J. Higham, S. Chou, F. Gräter, R. H. Henchman, Mol. Phys., 2018, 116, 1965.
[2] H. S. Ali, J. Higham, R. H. Henchman, Entropy, 2020, 21, 750.
[3] H. S. Ali, A. Chakravorty, J. Kalayan, S. P. de Visser, R. H. Henchman, submitted.
[4] A. Chakravorty, J. Higham, R. H. Henchman, J. Chem. Inf. Model., 2020, 60, 5540.
Year(s) Of Engagement Activity 2021
URL http://www.ccpbiosim.ac.uk/entropy2021
 
Description Sweden Keynote Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I gave a keynote presentation on drug design to a specialist audience.
Year(s) Of Engagement Activity 2018
 
Description Talk at Bristol Scientific Club 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact I gave a presentation which covered the use of holographic tweezers to control 3D-printed micro tools as a 3D optical AFM. The audience was from a wide science and engineering background and I believe the talk was received with enthusiasm. One result was that I was invited to join this prestigious club.
Year(s) Of Engagement Activity 2017
 
Description Talk give in Oxford to Shanghai Tech 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact A talk was given on free energy calculations as part of a discussion to investigate joint operations between the university and Shanghai Tech.
Year(s) Of Engagement Activity 2018
 
Description Talk in Dundee 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact A talk to 50-60 scientists from the Dundee area that provoked some interesting ideas and discussion.
Year(s) Of Engagement Activity 2017
 
Description Talk in the Physics of Life - Physics of Medicine Network Launch Event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Launch event of the third network of Physics of Life funded by the three UKRI councils EPSRC, MRC, BBSRC, Rosetrees Trust and the Universities of York, Durham and Leeds
Year(s) Of Engagement Activity 2020
URL http://www.physicsoflife.org.uk
 
Description Talk on "Why is life so complicated, can my computer help"? at Edinburgh science festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Talk at Edinburgh science festival explaining how supercomputing helps us to understand molecular biology.
Year(s) Of Engagement Activity 2017
 
Description Talk on "Why supercomputing is like Christmas" for the Wanstrow Christmas Lectures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact I explain how supercomputers are used to help scientists at the annual Wanstrow Christmas Lectures, Wanstrow Village Hall, Somerset.
Year(s) Of Engagement Activity 2017
 
Description Training workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact 12 early career researchers (mainly a mixture of PhD students and PDRAs) attended a 1-day workshop in Leeds organised by CCPBioSim/HECBioSim to learn how to use the computational workflows package "Crossflow" that was developed during this grant. The objective was to raise awareness of the software and promote its usage on the national supercomputing service ARCHER2.
Year(s) Of Engagement Activity 2023
 
Description Training workshop on using TINKER with the AMOEBA force field 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact We arranged a one-day training workshop on using the AMOEBA force field in the context of the TINKER molecular dynamics software.
Year(s) Of Engagement Activity 2016
URL https://sites.google.com/site/amoebaworkshop/
 
Description UKQSAR Sept 2018 Meeting - Bromodomains and Drug design 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk on drug design given.
Year(s) Of Engagement Activity 2018
 
Description Vertex 2018 Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact An invited talk given to Vertex Pharmaceuticals.
Year(s) Of Engagement Activity 2018
 
Description Yale iGluR Poster Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Poster presentation to about 130 scientists in the field of glutamate research
Year(s) Of Engagement Activity 2017
 
Description YouTube Channel 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Recordings of CCPBioSim organised talks and training are shared on the YouTube Channel (with the speaker's permission). This allows anyone who missed the event or would like to review the material again to watch the video at any convenient time. We hope that this makes computational biology more accessable.
Year(s) Of Engagement Activity 2020,2021
URL https://www.youtube.com/channel/UCJLWsk2Hbhf09--POlR67Nw