CCPBioSim: Biomolecular Simulation at the Life Science Interface

Biomolecular simulation aims to provide quantitative, predictive models for molecular structural biology from the level of enzyme catalysis up to cells. Modelling helps us to better understand the information we obtain from our experiments, and can provide insight in situations where experimental information is unavailable. Molecular simulations are based based on well-defined physics, and complement experiments: the unique insight they provide gives molecular level understanding of how biological macromolecules function. Simulations have proved crucial in analysing protein folding and self-assembly, mechanisms of biological catalysis, and the importance of dynamics in biomolecular function. Biomolecular simulations contribute to drug development (e.g. in structure-based drug design and predictions of metabolism) and design of biomimetic catalysts, and in understanding the molecular bases of disease and drug resistance.

However, the complexity of biological molecules means that simulating them is extremely challenging, and remains an active areas of research internationally. CCPBioSim is the UK network of researchers that brings together expertise to support biomolecular simulators to perform the best calculations feasible within current scientific understanding and compute resources. We actively engage with the international community of biomolecular simulators, to ensure that the UK has access to the most up to date ideas and insights. We drive methodological developments to improve the state of the art and to integrate biomolecular simulation with emerging experimental tools. We embrace technological improvements that make our simulations faster, more accurate and accessible to a broader community of researchers. We engage with our community by organising conferences and training workshops, and we provide software that makes their simulations less challenging and more effective.

Academic Impact: We have delivered ~20 training workshops and 12 conferences since 2015, ranging from basic simulation practise up to the most advanced new methods for enhanced sampling. The enhances the quality of the research performed by CCPBioSim members, by exposing them to "state of the art" methods and techniques. Since advanced tools often become mainstream over time, a broad base of biomolecular simulations ultimately gain from this increased expertise. A number of our training courses in CCPBioSim2015-2020 were not anticipated in the original proposal, and were developed in response to an emergent need over a rapid timescale. An important aspect of our impact is that we are able to respond to community needs in an agile way.

Feedback from attendees at workshops has also directly fed into our software development programme. For example, we are including enhanced sampling tools in BioSimSpace, at the request of the community. Our joint CCPBioSim/CCP-EM workshop on "Computation for Biomolecular Cryo-Electron Microscopy and Tomography" received particularly positive feedback for being the first of its kind. Feedback on the usability of the software tools has been fed into future software development plans.

Our software development programme aims to provide a broad portfolio of simple tools to the community, and to build on previous work by the MG. This emphasis is on good documentation, training materials and dissemination. The software tools developed will be followed up by a user workshop that employs them, to get user feedback. We will also invite our community to propose short (6 month) software development projects. As well as providing new software tools, such projects improve awareness of good software development practice throughout the community, which increases their impact.

Industrial and Societal Impact: Biomolecular simulation and modelling is vital e.g. to the pharmaceutical and agrochemical industries, 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). CCPBioSim contributes directly to both of these key requirements. Several members of our management group have strong links with these industrial sectors. Software developed by CCPBioSim (FEsetup, BioSimSpace) has been adopted by several pharmaceutical and life science software companies in the UK (UCB, Astra Zeneca, GSK, Syngenta, Cresset) and beyond (Janssen, Merck, Silicon Therapeutics, Qulabs) to support internal R&D processes and commercial software, helping boost the productivity and competitiveness of high-value sectors of the UK economy.

Longer term, CCPBioSim has the potential to contribute to improvements in health and quality of life via applications of the methodologies fostered and disseminated by CCPBioSim to drug discovery and biocatalyst manufacturing. Arguably, the biggest problem in structure based drug-design is our limited understanding of the role of biomolecular dynamics, which is a key area for CCPBioSim.

CCPBioSim also promotes innovative approaches (e.g. virtual reality) to disseminate chemical knowledge to the broader public via public engagement activities (e.g. science festivals in Edinburgh, and Bristol). We have early stage collaborations using VR interactive demos at our training weeks and conference, and will be investigating public engagement possibilities (e.g Astbury Conversation, Science festivals) when the technology is sufficiently mature. We are also exploring collaborations with computational artists (e.g. at Goldsmiths) to develop workshops that use biomolecular simulation to provide a scientific framework for artists and designers.