Expanding the limits of biomolecular simulations: revealing the mechanisms of blood clot formation using Fluctuating Finite Element Analysis.
Lead Research Organisation:
University of Leeds
Department Name: Physics and Astronomy
Abstract
Computational simulation of biomolecules has proven to be a very useful approach during the past few decades, and is now considered essential in broad range of disciplines ranging from the molecular understanding of life to drug discovery. Molecular dynamics is so frequently used to calculate the dynamic behaviour of proteins at the atomistic level firstly due to the large number of protein crystal structures that are publicly available in the Protein Data Base, but also because this methodology is well established, and excellent software packages are freely available to the academic biomolecular sciences community. However, we are still far from simulating cellular dimensions and time scales of entire biological processes. This will not be solved by hardware improvements in the foreseeable future, especially as the continuous increase
in computational power is slowing and may come to an end. As a consequence, new methodologies are needed to reach longer time- and length-scales.
This fellowship proposes to join two cutting edge methodologies in coarse-grained protein modelling to overcome this situation. Specifically,
I will work with the Fluctuating Finite Element Analysis that models proteins as a non-rigid continuum subjected to thermal fluctuations, and the Multi-Scale Coarse-Graining method that aims to describe simplified molecular interactions using a physically-based bottom-up approach.
Once this methodology is ready, I will implement it within a scalable piece of software suitable for High Performance Computing, and will use this new tool to simulate the fibrin network self-assembly process, one of the key events in clot formation. This is a highly important biological system, as in vivo imbalance is related to a number of human pathologies, including heart and brain infarction. Structural data on the clot architecture has been shown to correlate with clinical data on cardiovascular diseases.
I will use currently available experimental data to demonstrate the capabilities of the proposed methodology and software. Next, further simulations will shed light on association pathways and affinities leading to fibrin polymerisation, on the process of lateral aggregation of protofibrils, on the role of each of the known interaction sites, on the influence of the external flow, and on the effect that some pathological mutants have on the self-assembly process and the final structure of the clot.
Full accomplishment of these objectives will result in significant advances in biomolecular modelling methodology, together with the release of a general purpose application for biomolecular simulations on the mesoscale, and medically relevant results on the clot formation process and structure.
in computational power is slowing and may come to an end. As a consequence, new methodologies are needed to reach longer time- and length-scales.
This fellowship proposes to join two cutting edge methodologies in coarse-grained protein modelling to overcome this situation. Specifically,
I will work with the Fluctuating Finite Element Analysis that models proteins as a non-rigid continuum subjected to thermal fluctuations, and the Multi-Scale Coarse-Graining method that aims to describe simplified molecular interactions using a physically-based bottom-up approach.
Once this methodology is ready, I will implement it within a scalable piece of software suitable for High Performance Computing, and will use this new tool to simulate the fibrin network self-assembly process, one of the key events in clot formation. This is a highly important biological system, as in vivo imbalance is related to a number of human pathologies, including heart and brain infarction. Structural data on the clot architecture has been shown to correlate with clinical data on cardiovascular diseases.
I will use currently available experimental data to demonstrate the capabilities of the proposed methodology and software. Next, further simulations will shed light on association pathways and affinities leading to fibrin polymerisation, on the process of lateral aggregation of protofibrils, on the role of each of the known interaction sites, on the influence of the external flow, and on the effect that some pathological mutants have on the self-assembly process and the final structure of the clot.
Full accomplishment of these objectives will result in significant advances in biomolecular modelling methodology, together with the release of a general purpose application for biomolecular simulations on the mesoscale, and medically relevant results on the clot formation process and structure.
Planned Impact
The proposed research will produce three main deliverables. Firstly, there will be simulation results revealing the mechanisms of the molecular basis of fibrin clot formation. Secondly, a scalable piece of software to simulate proteins at the mesoscale will be released. And thirdly, physics based methodology on protein-protein interaction modelling. The impact of these deliverables will target the Healthcare sector, essentially through pharmaceutical industry. The implicit generality of methodological research will enable me in the future to consider applications such as the discovery of new bio-materials and the design of vehicles for drug delivery. Both of these areas of biotechnology are active areas of experimental research at Leeds.
Understanding fibrin clot formation has direct clinical implications in bleeding and thrombotic complications of several diseases. For instance, commonly used medications to prevent thrombosis have turned out to have secondary effects on the final structure of the clot, resulting in a susceptible to lysis clot. On the contrary, there is a new generation of specific drugs that target and modulate the so called "knob-hole" interactions (see fig. 2 in the case for support), mostly avoiding such secondary effects. While the importance of these interaction sites have been revisited, the proposed research will be able to assess the consequences that the modulation of all the interaction sites involved in the fibrin self-assembly process, have on the overall mesh structure.
International pharmaceutical companies that can be potentially interested in the fibrin results include Enzyme Research Laboratories, GEHT, George King Bio-Medical Inc., Haematologic Technologies Inc., and Biopur while others like BAYER, novo nordisk, Grifols, Kedrion Biopharma, Octa Pharma, Immucor are known to have R&D departments more generally focused on Thrombosis and Haemostasis. More generally, in silico methods like Virtual Screening have been crucial to decrease the costs of the pharmaceutical research. The software and methodology proposed to parameterise the interactions will extensible to other protein systems, with applicability in the pre-discovery phase to obtain new compounds. In addition, it could be used to expand the amount of known targets, as currently 50% of them belong to 4 families: GPCRs, nuclear receptors, ligand-gated ion channels, voltage-gated ion channels. In a next future, it could be applied to model and design drug delivery liposomes, both with specific surface ligands, as well as with the desired rhelogical properties. In summary, the deliverables of the proposed fellowship will become directly relevant to the drug research and hence of interest for pharmaceutical industry.
As published in Forbes[1], the pharmaceutical industry destroyed nearly 300,000 jobs in the 2000 to 2011 period, and their efficiency in R&D has been declining during decades, with the number of new drugs per billion US dollar being reduced by a factor of 80 since 1950[2]. With an ageing society, increasingly dependent on new medicines, this has become a public major concern as is reflected in the EPSRC Healthcare
Technologies theme. The proposed research is an excellent exponent of the impact that basic research has on the health and quality of life.
References:
[1] M. Herper, A decade in drug industry layoffs, 2011, available at:
http://www.forbes.com/sites/matthewherper/2011/04/13/a-decade-in-drug-industry-layoffs.
[2] J. W. Scannell et al., Nat Rev Drug Discov 11, 191 (2012).
Understanding fibrin clot formation has direct clinical implications in bleeding and thrombotic complications of several diseases. For instance, commonly used medications to prevent thrombosis have turned out to have secondary effects on the final structure of the clot, resulting in a susceptible to lysis clot. On the contrary, there is a new generation of specific drugs that target and modulate the so called "knob-hole" interactions (see fig. 2 in the case for support), mostly avoiding such secondary effects. While the importance of these interaction sites have been revisited, the proposed research will be able to assess the consequences that the modulation of all the interaction sites involved in the fibrin self-assembly process, have on the overall mesh structure.
International pharmaceutical companies that can be potentially interested in the fibrin results include Enzyme Research Laboratories, GEHT, George King Bio-Medical Inc., Haematologic Technologies Inc., and Biopur while others like BAYER, novo nordisk, Grifols, Kedrion Biopharma, Octa Pharma, Immucor are known to have R&D departments more generally focused on Thrombosis and Haemostasis. More generally, in silico methods like Virtual Screening have been crucial to decrease the costs of the pharmaceutical research. The software and methodology proposed to parameterise the interactions will extensible to other protein systems, with applicability in the pre-discovery phase to obtain new compounds. In addition, it could be used to expand the amount of known targets, as currently 50% of them belong to 4 families: GPCRs, nuclear receptors, ligand-gated ion channels, voltage-gated ion channels. In a next future, it could be applied to model and design drug delivery liposomes, both with specific surface ligands, as well as with the desired rhelogical properties. In summary, the deliverables of the proposed fellowship will become directly relevant to the drug research and hence of interest for pharmaceutical industry.
As published in Forbes[1], the pharmaceutical industry destroyed nearly 300,000 jobs in the 2000 to 2011 period, and their efficiency in R&D has been declining during decades, with the number of new drugs per billion US dollar being reduced by a factor of 80 since 1950[2]. With an ageing society, increasingly dependent on new medicines, this has become a public major concern as is reflected in the EPSRC Healthcare
Technologies theme. The proposed research is an excellent exponent of the impact that basic research has on the health and quality of life.
References:
[1] M. Herper, A decade in drug industry layoffs, 2011, available at:
http://www.forbes.com/sites/matthewherper/2011/04/13/a-decade-in-drug-industry-layoffs.
[2] J. W. Scannell et al., Nat Rev Drug Discov 11, 191 (2012).
People |
ORCID iD |
| Albert Crusat (Principal Investigator / Fellow) |
Publications
Solernou A
(2018)
Fluctuating Finite Element Analysis (FFEA): A continuum mechanics software tool for mesoscale simulation of biomolecules.
in PLoS computational biology
| Description | I have developed a new software tool to perform dynamic simulations of large protein assemblies based on low resolution structural information such as those provided by Electron Microscopy. In developing the software a new energy term was introduced in order to avoid the overlapping of the different bodies (steric repulsion) that is fast to compute and numerically stable, thus allowing longer and more stable simulations. These methodologies and their software implementation are publicly available under free license (GPL), and being physics-based, they can be used to study any system (bio and non-biological) that is big enough for the individual atoms to be averaged, and small enough for thermal fluctuations to be important. |
| Exploitation Route | I consciously put a lot of effort in documenting all my work, in providing ways to replicate the results, and in disseminating them. Thus, there is a web site where the software can be found, with documentation for developers and users, tools to build the software easily, binaries that can be downloaded, and a paper where rigorous physical mathematics are introduced with intuitive physical explanations. Two PhD students finished his PhD after I left, another one is about to finish and there are now another two, every one of these users or developers of FFEA. Furthermore, I know of one research group who started using FFEA without us having personally introduced it. I takes time for a new approach to consolidate, but I am very hopeful that the findings will be used and taken forward by others, and that my works are making a difference in the early adoption of the new approach that is FFEA. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| URL | http://ffea.readthedocs.io/en/latest/ |
| Description | A first attempt to parallelise FFEA using MPI |
| Organisation | University of Edinburgh |
| Department | Edinburgh Parallel Computing Centre (EPCC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I helped the student to compile FFEA on Archer, wrote FFEA documentation on usage, development and installation, and prepared a new system (a number of input files) to be used to find performance bottlenecks in FFEA and to benchmark a future parallel implementation of the FFEA. |
| Collaborator Contribution | Guanhao Lu made his master thesis at EPCC under the supervision of Toni Collis, studying the performance of FFEA and implementing a distributed memory parallel computing approach (MPI) on the interactions double loop (all to all within a cutoff). |
| Impact | A first MPI version of FFEA was delivered, its performance discussed in Guanhao Lu's MSc dissertation: https://static.ph.ed.ac.uk/dissertations/hpc-msc/2015-2016/Guanhao_Lu-MSc-dissertation.pdf The resulting version of the code is able to run on multiple nodes (different computers) in parallel, although it does not scale well, because only one section was parallelised. Nonetheless, this first approach served as the basis for a new proposal to parallelise FFEA. More explicitly, Sarah Harris, Toni Collis, and myself put in an eCSE proposal: http://www.archer.ac.uk/community/eCSE/ that was submitted recently with letters of support from CCP-BioSim and CCP-EM communities. |
| Start Year | 2016 |
| Description | FFEA performance assessment |
| Organisation | Numerical Algorithms Group Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | I submitted a service request to Performance Optimisation and Productivity (POP): https://pop-coe.eu/request-service-form to audit the performance of FFEA. I prepared a benchmark (a set of input files to simulate a molecular system) ensuring that it was stressing all parts of the code, so that the performance analysis would report on every different function. I was also introducing the usage of FFEA, and helping with some related problems. I addressed most of the issues raised by the resulting report from POP, increasing the performance of our code. |
| Collaborator Contribution | Jonathan Boyle in collaboration with Nick Dingle and Sally Bridgwater, all of them working at NAG, run a number of simulations using the setup I provided studying the scalability, efficiency, computational performance and load balance. |
| Impact | A report on the computational performance of FFEA was delivered by the team at NAG, pointing to some bottlenecks. Consistently, I tackled these, writing a faster and more robust version of FFEA that was soon released under a GPL licence. |
| Start Year | 2016 |
| Description | Investigating the parallel performance of the Fluctuating Finite Element Analysis tool |
| Organisation | University of Edinburgh |
| Department | Edinburgh Parallel Computing Centre (EPCC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I provided many explanations, and a number of input files to simulate different systems with different characteristics, making easy to Jana Boltersdorf to benchmark and study the computational performance of the FFEA code. Weekly meetings were held to help. |
| Collaborator Contribution | Jana Boltersdorf, who was a summer student at the EPCC, worked on characterising the performance of the FFEA code, which is being developed in our group, and provided a series of speed up plots as well as a final report. |
| Impact | - A series of speed-up charts where the run time of FFEA was measured using an increasing number of processors |
| Start Year | 2015 |
| Description | Visualisation of proteins using Paraview |
| Organisation | University of Edinburgh |
| Department | Edinburgh Parallel Computing Centre (EPCC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I provided a number of challenges on visualising FFEA trajectories using Paraview. Using Paraview (http://www.paraview.org/) was proposed after I found our current viewer to perform poorly on medium and large sized systems, and after finding the limitations that VMD (http://www.ks.uiuc.edu/Research/vmd/) had in handling our sort of trajectories. In addition, I provided a number of systems to be visualised (input files) and weekly meetings were held sharing ideas and giving advice. |
| Collaborator Contribution | Ondrej Vysocký, who was a summer student at EPCC under the supervision of Dr Toni Collis and Dr Neelofer Banglawala , wrote a python script to convert FFEA trajectories into VTK format. They could then be read by Paraview, and Ondrej provided with a number of recipes to display different attributes, making easier to visualise simulation output trajectories. |
| Impact | - A FFEA to VTK file converter written in Python. - A number of recipes to visualise VTK trajectories using Paraview. |
| Start Year | 2015 |
| Title | FFEA |
| Description | The FFEA (Fluctuating Finite Element Analysis) is a software tool that intends to simulate large molecular systems as viscoelastic solids subject to thermal noise. The software consists of two parts, the 'runner' and the 'tools'. The runner is the part that simulates the dynamics of a molecular system given a set of input files. The 'tools' are a set of small programs that help the user through all the FFEA work-flow, together with a plugin for PyMOL for visual inspection of the systems and the resulting trajectories. Besides coding and working on the performance of the runner, I have been working on other aspects of the code release. The code has been documented, both from the user and from the developer perspectives using Doxygen and Markdown, and a tutorial has been written, all resulting in a nice web site. A test suite has been included, where short simulations of simple systems are compared to known analytical results, aiming to ensure that the physics is correctly reproduced. Finally, the building and installation processes have been fully automated using CMake, while binaries are also provided for Linux x86 64bit platforms. |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | I am not aware of any notable impacts resulting from the development of this software yet. However, I worked very hard to accelerate the adoption of the new approach as it is presented in numerous entries of the Engaging Activities. Thus, in "FFEA Practical Workshop", we successfully run a single day workshop on FFEA on July 2017 promoting the use of the approach. Moreover, in "CCPEM Developers Meeting", it was agreed that FFEA should be included within the CCP-EM software stack. Finally, in "CompBioMed All-Hands Meeting 2017", I convinced the CompBioMed Center of Excellence of seeking new funds for further developing the methodologies. Furthermore, we wrote a paper in PLOS Computational Biology that has already been accepted and that should be out very soon, presenting the approach in a very accessible way, together with a rigorously mathematical appendix. I honestly expect that all this efforts make a difference at this early stage for the community to adopt the FFEA as a new valid approach. |
| URL | http://ffea.readthedocs.io/en/stable/ |
| Title | Volume overlapping steric repulsion algorithm for continuum mechanics simulation |
| Description | I designed and implemented the volume overlapping steric repulsion algorithm in FFEA as a new method to deal with contact interactions. Accordingly, bodies feel a steric repulsion energy that is proportional to their overlapping volume, resulting into a repulsion force that is applied at the center of the overlapping volume. The force is calculated numerically as the negative gradient of this energy. Because volume is an extensive quantity, the calculation of this volume can be split into a number of parts and summed up. Furthermore, the resulting force does not depend on any path, and so it is a conservative force. The description of this force was presented also in the PLOS Computational Biology paper together with the FFEA software package. |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | The FFEA was previously modelling short range interactions using a Lennard-Jones potential, using a Gaussian quadrature scheme. However, that was often leading to a very strong force resulting making the simulation to explode. The new approach is much more stable, allowing significantly larger time steps (between 10 and 100 times larger), thus resulting in larger and longer simulations. |
| URL | https://bitbucket.org/FFEA/ffea/src/d148a358bcf82262631d5101dd5d29ae6d151e6d/src/VdW_solver.cpp?at=m... |
| Description | Advanced Research Computing User Meeting (Leeds) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave a talk entitled "Simple tricks to improve the performance: a real case study" in the Advanced Research Computing User Group. The meeting brings periodically together the users of the main computer cluster of the University of Leeds, and in that talk I showed what I had done, with minimal effort to improve the performance of the code that I use to simulate proteins dynamics. I was the first user reporting and showing the usage of the Allinea MAP, a powerful software profiler that the University had purchased recently, motivating new users to try it. In addition, there was a nice discussion on other approaches I could considerate to improve even more the performance of the code at a low cost. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Astbury Conversation (Leeds) |
| 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 poster at this short conference engaging 250 scientist from all over the world. People who I talk to includes Nobel laureate Michael Levitt who made reference to our work later in his talk. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.astburyconversation.leeds.ac.uk/symposium.php |
| Description | British Science Week at Horsforth Featherbank Primary School |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Celebrating the British Science Week, I gave a talk about "Computational Physics for Biomolecular Modelling" to Year 2 children at the Horsforth Featherbank Primary School (Leeds). Aiming to promote scientific thinking and physics on top of it, I presented the different fields in which physics has been successful in developing a theory, and showing how theories have been evolving in time, all connecting to each other progressively, up to the ultimate missing unification, where General Relativity should link to the Standard Model. Later I presented the field of biophysics, and focused in molecular and cell modelling from a physics perspective, showing some of my works in the field. The children were very curious on the every day life of a scientist, such as the hours worked, what if I was forced to move to another job, et cetera. |
| Year(s) Of Engagement Activity | 2017 |
| Description | CCPBioSim/CCP5 Multiscale Modelling Conference (Manchester) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The conference brought together international leaders in a number of research areas, from fundamental physics to materials and biology, sharing interest in multi-scale modelling. I presented a poster in the conference, which was well received, and the discussion arising from the very creative and different approach was truly enriching. |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://eventbooking.stfc.ac.uk/news-events/second-ccpbiosimccp5-conference |
| Description | CCPEM Developers Meeting |
| 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 | The Collaborative Computational Project for Electron Microscopy (CCP-EM) supports users and developers in cryo-microscopy. Thus, its principal aims are: to build a UK community for computational aspects of cryo-EM, to support the users of software for cryo-EMthrough dissemination on available software and directed training, and to support for software developers including porting, testing, and distribution of software. In this developers workshop I gave a talk presenting our works on FFEA, with special focus on the methods and the software implementation, seeking integration within the community. The meeting was very successful in supporting our works, as it concluded that that FFEA should become part of the software stack that CCP-EM distributes. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Combining Simulation and Experiment in Molecular Imaging (Southampton) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | I presented FFEA, the modelling approach that we are developing in Leeds, to an audience mainly composed of postgraduate students with a biology background. The main aim was to show how the latest low resolution imaging techniques can be combined with molecular simulation. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.southampton.ac.uk/ifls/news/events/2016/05/25-molecular-imaging.page |
| Description | CompBioMed All-Hands Meeting 2017 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | CompBioMed is a European Centre of Excellence that, with partners in Industry and Academia, aims to provide computational solutions for specific medical problems. Therefore, they are interested in covering the whole scale in the human body, from the molecular to the macroscopic. In order to cover the existing gap between these to description levels, I was invited to give a talk about my works on FFEA and on modelling mesoscopic systems. My presentation raised serious interest and we were talking about including this approach within the CoE, at their next phase in mid 2018. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.compbiomed.eu/events-2/all-hands-meeting-2017/ |
| Description | European Biophysical Society Association Congress (Dresden) |
| 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 poster entitled "Understanding fibrin protofibrils at the molecular level through a new coarse-grained approach" at the European Biophysical Society Association Congress. There were several very interesting discussions, some of them methodological and explicitly on different coarse-grained approaches (so in the field that I am doing research) and some of them on fundamental biophysical processes that would benefit enormously if using the meso-scale approach that I am developing. Extremely useful. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://ebsa.org/ebsa-2015 |
| Description | FFEA Practical Workshop |
| 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 | FFEA provides an equivalent simulation tool for the Electronic Microscopy Data Base (EMDB) as atomistic MD simulations does for the PDB. Using volumetric information rather than atomistic co-ordinates as input it can model protein dynamics, protein-protein interactions, or conformational switching between known configurational states and can be mapped back to atomistic co-ordinates, where these are available. Therefore, this workshop on FFEA targeted biomolecular simulators who would like to make full use of cryo-EM data in their modelling, or for experimentalists who would like to gain new theoretical insight into the dynamic behaviour of the structures they observe. We carefully prepared materials on setting up systems from EMDB surfaces, modelling their interactions, and visualisation and analysis of the results, showing the strengths and the flexibility of the approach. The workshop run on a Linux OS, running from a USB stick, where the environment, dependencies, and 3rd party packages together with the materials were carefully set. This USB stick was a present to the attendees, as an effective way to invite them to try the software in their organisations, aiming to maximise the impact of the event. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.ccpem.ac.uk/training/leeds_em_md_2017/leeds_em_md.php |
| Description | International Fibrinogen Workshop (Skukuza, South Africa) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The 4 days long fibrinogen workshop brought together the leading researchers of the field in an ideal environment for discussion and collaboration. I was presenting a poster on the types of calculations and modelling that we are working on, and it certainly was well received. A number of ideas came to me, and conversations for establishing future collaborations were started. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.nwu.ac.za/fibrinogen |
| Description | International on Thrombosis and Haemostasis (Toronto) |
| 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 poster entitled "Understanding Fibrin Protofibrils at the Molecular Level: Formation and Flexibility Through a New Coarse-Grained Protein Modelling Approach". The poster had a great reception as the conference attendees were mostly experimentalists, and most of them were working on larger and much larger time and length-scales. It was very stimulating to meet the experts that could use the theoretical approaches that I am developing, and see that they had high interest in my work. The same trip to Toronto was used to meet Régis Pòmes at the Sick Kids Hospital: http://biochemistry.utoronto.ca/person/regis-pomes/ to talk about future collaboration using FFEA to model a number of cellular processes involving aggregation. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://www.isth.org/mpage/2015Microsite |
| Description | N8-HPC Multiscale Computational Mechanics (Sheffield) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | I was selected to give an oral presentation entitled "A bottom-up approach to describe protein-protein interactions in a continuum mechanics biomolecular model" in this "Network Event" with the aim of bringing the regional researchers in Multiscale Computational Mechanics together. It was a very useful meeting as most of the attendees were engineers, and that gave me the opportunity to hear about a wide range of approaches used on different systems. In addition, the event was organised by the N8-HPC, which brought in the computational perspective. Truly multidisciplinary. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://n8hpc.org.uk/n8-hpc-network-event-multiscale-computational-mechanics/ |
| Description | Research Software Engineering Conference 2017 |
| 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 | The Research Software Engineering Conference aims to bring in together Research Software Engineers to share their experiences within research groups. In there, I gave a talk entitled "Strategies for correctness, performance and documentation in research software" where I talked about these topics as I had approached them in my works on FFEA. Thus, on correctness I introduced the test suite aiming to test the Physics in FFEA, as well as the tags that logging files had so that they could be related to their exact versions of the software, and the importance of using a statistically reliable Parallel Random Number Generator for the parallel computing. On performance, I talked about the dual approach that I implemented in FFEA for parallel computing, namely distributing the workload of the interactions of the system, and solving the equations of motion. Finally, on documentation I talked on how Doxygen was useful for me as programmer, but also on how it could be helpful to other programmers, on how to add extra documentation using Markdown, and on how to make this built automatically at every change in the code and hosted online through www.readthedocs.io. The slides can be found here: http://rse.ac.uk/conf2017/wp-content/uploads/sites/2/2017/11/Strategies_for_correctness_performance_and_documentation__ASolernou.pdf |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://rse.ac.uk/conf2017/ |
| Description | Workshop in Molecular Modelling and Simulation (Leeds) |
| 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 talk presenting our multi-scale model for molecular biology in the department of Chemistry of the University of Leeds, where Prof Carol Hall from North Carolina State University also presented her works on coarse-grained molecular modelling. The audience background was mixed, mostly from biology or chemistry. There was a very interesting final discussion involving Andrew Wilson from Chemistry, Carol Hall, Sarah Harris (from physics) and myself. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Workshop on Biophysical Modelling and Simulation (UCL, London) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a small single-day workshop where people from Peter Coveney's (UCL) and from Sarah Harris' (Leeds) groups presented their current work in a number of short talks. I gave a talk on the methodological work that I am doing, raising a great interest. There was a very interesting discussion about the convergence of the methodology with a direct effect on the decisions that I was taking afterwards on my research. In addition, Peter Coveney introduced his works on fluctuating hydrodynamics, which could help in the future at introducing hydrodynamics in our FFEA model, leading to future collaboration. |
| Year(s) Of Engagement Activity | 2015 |