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

生物分子模拟是一个快速发展的领域，对结构生物学和药物研究做出越来越重要的贡献。模拟有助于药物开发（例如，基于结构的药物设计和代谢预测），仿生催化剂的设计，以及了解疾病和耐药性的分子基础。CCP BioSim（ccpbiosim.ac.uk）在EPSRC的支持下于2011年成立，以加强生命/科学界面的分子模拟，并发展与学术界/工业界的联系。CCP-BioSim在2013年成功领导了EPSRC对生物分子模拟高端计算联盟HECBioSim（hecbiosim.ac.uk）的竞标。HEC-BioSim致力于为更广泛的实验学家社区带来高性能计算，并吸引物理科学家参与生物应用。CCP-/HECBioSim定期组织培训讲习班，并提供网络和协作框架。我们还致力于开发和应用先进的方法，并参与国际活动（例如NSF，CECAM，NIH等）。我们积极与结构和化学生物学家和工业研究人员通过合作，传播和应用软件，并邀请会议和研讨会。我们通过联合研讨会和会议积极与其他CCP合作。我们积极支持社区软件开发，并发布了软件，使生物分子模拟更容易为不同的社区所用。我们的领域受益于HPC和化学物理学的不断进步（例如多尺度建模，2013年诺贝尔化学奖）。我们的技术已经达到了一个阶段，我们现在的目标是全面改变分子设计科学。制药公司不断寻求设计新药来治疗例如抗菌感染或癌症。农用化学品公司不断寻求新的化学品来治疗害虫，支持农业增长，为我们的人口提供粮食。生物分子设计是一个复杂的多目标优化问题。为了取得重大进展，我们的领域越来越多地将多个软件包结合到工作流程中。这与我们领域的历史范式不同，在我们的领域中，研究问题一次用一种或几种技术来解决。我们的社区缺乏软件来轻松地将我们的工具组装成解决分子设计科学所需的强大，可扩展和全面的工作流程。作为CCP-/HECBioSim旗舰社区软件项目，我们建议开发BioSimSpace。我们的软件将提供一个互操作性层，允许来自我们社区的软件包一起工作。翻译工具将确保一个软件包的输出可以很容易地用作另一个软件包的输入。重要的是，BioSimSpace将使工作流程的组件能够独立于底层软件应用程序编写。这将允许将工作流组件混合并匹配到更复杂的工作流中，并为这些工作流选择最适合底层计算机硬件的应用程序。我们将使用BioSimSpace来验证新的工作流程，以解决筛选药物效价、结合途径和动力学的巨大挑战。通过与商业软件供应商合作，我们将使基于BioSimSpace的组件易于打包，以便它们可以通过软件市场轻松共享、安装和销售。通过与一系列国家和国际工业和学术合作伙伴合作，我们将开发和应用基于BioSimSpace的工作流程，以解决我们社区以及制药和农用化学品行业面临的分子设计问题。通过使用超级计算机，我们将展示大型BioSimSpace工作流程如何帮助降低为医疗保健和工业生物技术应用设计分子所需的成本和时间。

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.