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

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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.