EPSRC Flagship Software - BioSimSpace: A shared space for the community development of biomolecular simulation workflows

Biomolecular simulation is a fast growing area, making increasingly important contributions to structural biology and pharmaceutical research. Simulations contribute to drug development (e.g. in structure-based drug design and predictions of metabolism), design of biomimetic catalysts, and in understanding the molecular basis of disease and drug resistance.

CCP-BioSim (ccpbiosim.ac.uk) was established in 2011 with support from EPSRC to strengthen molecular simulations at the life/sciences interface, and develop links with academia/industry. CCP-BioSim led in 2013 a successful EPSRC bid for a High-end Computing consortium in Biomolecular simulation, HECBioSim (hecbiosim.ac.uk). HEC-BioSim works to bring high-performance computing to a wider community of experimentalists and to engage physical scientists in biological applications. CCP-/HECBioSim regularly organize training workshops and provide a framework for networking and collaboration. We also work to develop and apply advanced methods, and engage with international activities (e.g. NSF, CECAM, NIH etc.). We actively engage with structural and chemical biologists and industrial researchers through collaboration, dissemination and application of software, and invitations to conferences and workshops.
We actively collaborate with other CCPs via joint workshops and conferences. We actively support community software development and have released software to make biomolecular simulations more accessible to diverse communities.

Our field benefits from continuous advances in HPC and chemical physics (e.g. multiscale modelling, 2013 Nobel Prize in Chemistry). Our techniques have reached a stage where we now aim to comprehensively transform the science of molecular design. Pharmaceutical companies continuously seek to design new drugs to treat e.g. antibacterial infections or cancers. Agrochemical companies continuously seek new chemicals to treat pests, supporting agricultural growth to secure food for our population. Biomolecular design is a complex multi-objective optimization problem. To make significant headways our field is increasingly combining multiple software packages into workflows. This departs from the historical paradigm of our field, where research problems were tackled with one or a few techniques at a time. Our community lacks software to easily assemble our tools into robust, scalable and comprehensive workflows needed to address the science of molecular design.

As a CCP-/HECBioSim flagship community software project, we propose to develop BioSimSpace. Our software will provide an interoperability layer to allow software packages from our communities to work together. Translation tools will ensure that outputs from one package can be easily used as inputs to another package. Importantly, BioSimSpace will enable components of a workflow to be written such that are independent of the underlying software application. This will allow workflow components to be mixed and matched into more complex workflows, and for those workflows to select applications that will be optimal for the underlying computer hardware. We will use BioSimSpace to validate new workflows that address the grand challenges of screening drugs for potency, binding pathways and kinetics.

By working with a commercial software vendor, we will make it easy to package BioSimSpace-based components so that they can be easily shared, installed and sold via a software marketplace. By working with a range of national and international industrial and academic partners, we will develop and apply BioSimSpace-based workflows to address molecular design problems faced by our community, and the pharmaceutical and agrochemical industries. By using supercomputers we will demonstrate how large BioSimSpace workflows help decrease the costs and time needed to design molecules for healthcare and industrial biotechnology applications.

Molecular design of new classes of materials and medicines is vital to help address societal challenges via technological advances. Computer simulations play an increasingly important role in enabling the rational engineering of molecular structures for diverse applications. Continuous support is needed to maintain the UK's lead in this area. Good computer simulations depend on robust software. Modern molecular design challenges are complex and multi-objectives, and no single piece of software can model all relevant physical processes. Workflows that chain together multiple pieces of software offer an elegant solution, but their robust implementation currently is a major bottleneck owing to the lack of compatibility between community software packages. This research will deliver tools and exemplar workflows to empower the broader biomolecular simulation community to contribute computational solutions to current and emerging challenges posed by molecular design.

This work will benefit the pharmaceutical and associated chemical industries that have a long history of benefiting from tools and techniques developed by the biomolecular simulation community. Scientists working in industry will be interested in re-using the protein-ligand binding affinity and binding kinetics workflows developed during this project to support early stage drug discovery research. This will equip the industry with new tools to pursue solutions for urgent societal challenges, for instance new therapeutics to address the rise of antimicrobial drug resistance, or more effective drug therapies for neurodegenerative diseases. Because the workflows will be built upon modular and interoperable components, scientists will be able to adapt and reuse these workflows for related activities, for instance materials or soft-condensed matter engineering. This work will encourage greater adoption of HPC in industrial molecular design, thus helping develop the contribution of this IT sector to the UK's economy.

Through its direct industrial applications, the proposed work has the potential to impact on public healthcare costs by helping deliver effective therapies to keep the public in good health. The development and manufacturing of new pharmaceuticals and IT infrastructures are key activities for the UK economy, bringing significant benefits to local communities. Through indirect contributions to the vitality of these economic sectors, this research will also contribute to the prosperity of the country.