HECBioSim: The UK High End Computing Consortium for Biomolecular Simulation.

生物分子模拟使我们能够预测给定组件结构(或模型)的生物系统的行为。结合结构生物学和机器学习方法的新进展，分子模拟为深入了解生物分子系统提供了前所未有的空间。这些方法提供的详细程度，加上它们对实验数据进行合理化和扩充的能力，以及它们在生成新假设方面的预测能力，已经使它们能够在对医疗保健、环境、生活质量以及经济至关重要的广泛领域做出重大贡献。英国生物分子模拟界在国际上享有盛誉，在药物设计和开发、生物催化、生物纳米技术、化学生物学和医学方面的研究处于世界领先地位。最近我们的工作证明了这一点，我们的工作对SARS-CoV2病毒的研究产生了巨大影响，在帮助确定疫苗和抗病毒开发的目标位置方面，并使我们的成员赢得并入围国际奖，与行业合作伙伴建立新的合作伙伴，并成为大型国际财团的关键参与者。此外，除了我们在新冠肺炎上的工作外，我们还在生物芯片技术、药物设计、AMR以及开发新模型(例如波动有限元模型)方面开展了具有影响力的杰出研究。方法(例如，细粒度和粗粒度分辨率之间的转换)和使能技术(例如，有效提交计算的工具)，以便在生物物理和生化科学的全部范围内应用。就我们的工作范围而言，我们现在正处于可以实现巨大飞跃的时候。要做到这一点，拥有英国最大、最现代化的计算设施是至关重要的。该联盟的续签将使我们能够继续为我们的尖端生物分子模拟分配时间ARCHER2和Tier 2资源。我们将特别重视接触实验者(事实上，我们在这方面已经享有很高的声誉)和在行业工作的科学家，以促进计算和实验科学家之间的互动，以及学术界和工业界之间的互动，以鼓励对关键问题的综合多学科研究。生物分子模拟是药物设计和开发不可或缺的一部分。制药业需要在这一领域训练有素的科学家，以及开发新的方法(例如，预测药物结合亲和力、配体选择性和新陈代谢)。该联盟的成员在与工业界合作提供训练有素的科学家和新方法方面有着良好的记录。例如，由财团成员培养的博士生最近在联合银行、联合利华、牛津纳米孔技术公司和埃克斯塔公司任职。许多这样的学术和行业合作得到了加强，在某些情况下，是在通过HECBioSim分配所做工作的基础上建立起来的。财团将继续欢迎来自全社会的新成员，包括ECR。事实上，我们在担任独立学术职位方面，一直以来都有良好的纪录。我们将继续利用HEC资源的生物分子模拟为专家和非专家开发计算工具和培训。我们建议开发新的工具，通过利用机器学习领域的工具来实现更高效的模拟，并使用我们自己的代码来增强它们，以最大限度地利用英国HEC环境。总而言之，HECBioSim将扩大我们与实验科学家和工业工作人员的合作努力组合，以利用所有领域的专业知识为我们自己的工作提供信息，从而保持英国在生物分子模拟方面的世界领先地位。

Biomolecular simulations enable us to predict the behaviour of biological systems given the structures (or models) of the components. Combined with the structural biology and new advancements in machine learning methods, molecular simulations provide the scope for unprecedented insights into biomolecular systems. The level of detail afforded by these methods, along with their ability to rationalise and augment experimental data and their predictive power in generating new hypotheses are already enabling them to make significant contributions in a wide variety of areas that are crucial for healthcare, the environment, quality of life and consequently, to the economy. The UK biomolecular simulation community has a strong international reputation, with world-leading research in in drug design and development, biocatalysis, bionano-technology, chemical biology and medicine. This has recently been demonstrated by the enormous impact our work has made on research into the SARS-CoV2 virus, in helping identify target sites for vaccine and antiviral development and has lead to our members winning and being shortlisted for international prizes, establishing new collaborations with industrial partners and being key participants in large international consortia.Furthermore, in addition to our work on Covid-19, we have delivered outstanding research with impact in bionanotechology, drug design, AMR as well as in developing novel models (e.g. fluctuating finite elements models), methodologies (e.g. conversion between fine-grained and coarse-grained resolutions) and enabling technologies (e.g.tools for efficient submission of calculations) for application across the full spectrum of biophysical and biochemical sciences. We are now at a time when we can take giant leaps in terms of the scope of our work. Having access to the largest, most modern computing facilities in the UK is essential for this. Renewal of the Consortium will enable us to continue allocating time ARCHER2 and Tier 2 resources for our cutting-edge biomolecular simulations.We will place a special emphasis on reaching out to experimentalists (indeed we already have a strong reputation for doing this) and scientists working in industry in order to foster interactions between computational and experimental scientists, and academia and industry to encourage integrated multidisciplinary studies of key problems.Biomolecular simulation is an integral part of drug design and development. The pharmaceutical industry needs well-trained scientists in this area, as well as the development of new methods (e.g. for prediction of drug binding affinities, ligand selectivity and metabolism). Members of the consortium have a strong track record of collaboration with industry to deliver trained scientists and new methodologies. For example, PhD students trained by consortium members have recently taken up positions in UCB, Unilever, Oxford Nanopore Technologies and Exscientia. Many of these academic-industry collaborations have been strengthened and in some cases, been established on the basis of work done through HECBioSim allocations. The Consortium will continue to welcome new members from across the whole community including ECRs. Indeed we have an excellent track record of ECRs from within our community going on to independent academic posts. We will continue to develop computational tools and training for both experts and non-experts using biomolecular simulation on HEC resources. We propose to develop new tools that will enable more efficient simulations by harnessing tools from the machine learning field an augmenting them with our own codes to make best use of the UK HEC landscape.In summary, HECBioSim will expand our portfolio of collaborative endeavours with experimental scientists and those working in industry to harness expertise from all domains to inform our own work and thus to maintain the UK as a world-leader in biomolecular simulation.