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

生物分子模拟使我们能够在给定组分结构（或模型）的情况下预测生物系统的行为。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范围。这些方法所提供的细节水平，以及它们合理化和增强实验数据的能力，以及它们在产生新假设方面的预测能力，已经使它们能够在各种领域做出重大贡献，这些领域对医疗保健、环境、生活质量乃至经济都至关重要。英国生物分子模拟界在国际上享有很高的声誉，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，我们的工作对SARS-CoV2病毒的研究产生了巨大影响，帮助确定了疫苗和抗病毒药物开发的靶点，并导致我们的成员赢得并入围国际奖项，与工业伙伴建立了新的合作关系，并成为大型国际联盟的主要参与者。此外，除了我们在Covid-19方面的工作外，我们还在生物纳米技术、药物设计、抗菌素耐药性以及开发新模型（例如波动有限元模型）、方法（例如细粒度和粗粒度分辨率之间的转换）和使能技术（例如高效提交计算的工具）方面取得了杰出的研究成果，在生物物理和生化科学的各个领域都有应用。我们现在处在一个可以在我们的工作范围上取得巨大飞跃的时期。因此，拥有英国最大、最现代化的计算机设备是至关重要的。联盟的续签将使我们能够继续分配时间ARCHER2和Tier 2资源，用于我们尖端的生物分子模拟。我们将特别强调与实验家（事实上我们在这方面已经有了很高的声誉）和在工业界工作的科学家接触，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，以鼓励对关键问题进行综合多学科研究。生物分子模拟是药物设计和开发的重要组成部分。制药业需要这一领域训练有素的科学家，也需要开发新方法（例如预测药物结合亲和力、配体选择性和代谢）。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，由联盟成员培养的博士生最近在UCB、联合利华、牛津纳米孔技术公司和Exscientia担任职位。许多这样的学术-工业合作得到了加强，在某些情况下，是在通过HECBioSim拨款所做的工作的基础上建立起来的。联盟将继续欢迎包括ecr在内的整个社区的新成员。事实上，我们有一个很好的记录，从我们社区的ecr到独立的学术职位。我们将继续开发计算工具和培训专家和非专家使用生物分子模拟HEC资源。我们建议开发新的工具，通过利用机器学习领域的工具，并利用我们自己的代码对其进行增强，以充分利用英国高等商学院的景观，从而实现更有效的模拟。总之，HECBioSim将扩大我们与实验科学家和工业界工作人员的合作努力组合，利用各个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领域的世界领先地位。

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.