CCP-BioSim: Biomolecular simulation at the life sciences interface

生物分子模拟是一个充满活力和不断发展的领域，对结构生物学和系统生物学的贡献越来越大。基于物理的模拟补充了在分子水平上对生物学的理解：它们可以测试假设，解释和分析原子水平上相互作用的实验数据。各种各样的模拟技术已经被开发出来，适用于生物分子科学中的一系列不同问题。模拟已经显示出它们在帮助分析酶如何催化生化反应，以及蛋白质如何采用其功能结构（例如在细胞膜内）方面的价值。它们有助于药物和催化剂的设计，并有助于了解疾病的分子基础。模拟在发展生物分子科学核心的概念框架方面发挥了关键作用，也就是说，理解生物分子运动和弯曲的方式——它们的动力学——是它们功能的核心。从化学物理和计算科学中发展方法将为生物分子科学，包括药物设计和开发，生物技术和生物催化开辟令人兴奋的新机会。许多生物分子模拟需要HPC资源：例如大规模模拟生物机器，如核糖体、质子泵和马达、膜受体复合物甚至整个病毒。一个特别的挑战是跨长度和时间尺度的模拟集成：不同类型的问题需要不同类型的模拟方法)。我们建议在生命科学接口上建立一个新的生物分子模拟协作计算项目，CCP-BioSim。cpc - biosim将是一个包容性广泛的项目，汇集了化学家，物理学家和化学工程师以及来自“分子导向”生物化学和生物学各个分支的研究人员。我们的目标是让实验学家和计算专家参与进来，共同相信，当理论和实验紧密结合时，最好的科学可以完成。我们将邀请所有现有的CCPB成员（超过300人）加入CCP-BioSim，以及任何其他感兴趣的研究人员。会员将通过cpc - biosim邮件列表和cpc - biosim网站获得活动通知。CCP-BioSim将致力于确定该领域的方法和计算挑战，并促进发展以应对这些科学挑战。早期职业学者的参与也将是一个重要目标：我们将举办的培训讲习班将有助于建立研究小组。cpc - biosim还将提供网络和协作框架。该战略将集中于促进和便利高影响力生物分子研究的活动。我们将促进计算和实验科学家之间的密切和创新的互动，鼓励综合多学科研究。CCP-BioSim将开发并提供培训和工具，以降低非专家成为熟练和高效的生物分子模拟技术用户的障碍。我们还将努力开发和应用先进方法。与实验人员的接触对于确保所提供的方法与生物学问题相关至关重要。这是一个快速发展的领域：在英国和国际项目的背景下，最好的科学来自新的模拟技术和最先进的（特别是高性能计算（HPC））硬件和软件，需要方法论的发展和重要的和多样化的软件开发工作。

Biomolecular simulation is a vibrant and growing area, making increasingly significant contributions to structural and systems biology. Physics-based simulations complement experiments in building a molecular level understanding of biology: they can test hypotheses and interpret and analyse experimental data in terms of interactions at the atomic level. A wide variety of simulation techniques have been developed, applicable to a range of different problems in biomolecular science. Simulations have already shown their worth in helping to analyse how enzymes catalyse biochemical reactions, and how proteins adopt their functional structures e.g. within cell membranes. They contribute to the design of drugs and catalysts, and in understanding the molecular basis of disease. Simulations have played a key role in developing the conceptual framework now at the heart of biomolecular science, that is, the understanding that the way that biological molecules move and flex - their dynamics - is central to their function. Developing methods from chemical physics and computational science will open exciting new opportunities in biomolecular science, including in drug design and development, biotechnology and biocatalysis. Much biomolecular simulation demands HPC resources: e.g. large-scale simulations of biological machines such as the ribosome, proton pumps and motors, membrane receptor complexes and even whole viruses. A particular challenge is the integration of simulations across length and timescales: different types of simulation method are required for different types of problems).We propose to establish a new collaborative computational project in biomolecular simulation at the life sciences interface, CCP-BioSim. CCP-BioSim will be an inclusive wide-ranging project, bringing together chemists, physicists and chemical engineers as well as researchers from all branches of 'molecule-oriented' biochemistry and biology. Our aim will be to involve experimentalists and computational specialists, sharing the belief that the best science can be done when theory and experiment are closely integrated. We will invite all current CCPB members (more than 300) to join CCP-BioSim, and also any other researchers who are interested. Members will be informed of activities via the CCP-BioSim mailing list and the CCP-BioSim website. CCP-BioSim will aim to identify methodological and computational challenges in the field, and to foster develoments to meet these scientific challenges. Involvement of early career academics will also be an important goal: the training workshops we will run will help in establishing research groups. CCP-BioSim will also provide a networking and collaboration framework. The strategy will be to concentrate on activities that promote and facilitate high-impact biomolecular research. We will foster close and innovative interactions between computational and experimental scientists, encouraging integrated multidisciplinary studies. CCP-BioSim will develop and provide training and tools to lower the barrier to non-experts becoming proficient and productive users of biomolecular simulation techniques. We will also work to develop and apply advanced methods. Engagement with experimentalists is crucial to ensure that the methodologies delivered are relevant to biological problems. This is a rapidly developing field: the best science comes from new simulation techniques and state-of-the-art (especially high performance computing (HPC)) hardware and software, requiring methodological development and significant and varied software development effort, in the context of UK and international projects.