CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface

CCP-BioSim：生命科学界面的生物分子模拟

基本信息

批准号：
EP/M022609/1
负责人：
Adrian Mulholland
金额：
$ 30.03万
依托单位：
University of Bristol
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FM022609%2F1
关键词：
CCP BioSim Biomolecular Simulation Life

项目摘要

"Everything that living things do can be understood in terms of the jigglings and wigglings of atoms" as Richard Feynman provocatively stated nearly fifty years ago. But how can we 'see' this wiggling and jiggling and understand how it drives biology? Increasingly, computer simulations of biological macromolecules are helping to meet this challenge. Experiments can provide detailed structures of biological macromolecules such as proteins, but it is hard to study directly how the structures of individual molecules change on short timescales as they function. Similarly it is not yet possible to study directly by experiment alone the molecular mechanisms of fast processes such as chemical reactions in enzymes or ion transport through membranes. Simulations based on fundamental physics offer the potential of filling-in these crucial 'gaps', modelling how proteins and other biomolecules move, fluctuate, interact, react and function.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. They can help in the design of drugs and catalysts, and in understanding the molecular basis of disease. And 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, demonstrating the truth of Feynman's assertion.Developing methods from chemical physics and computational science will open exciting new opportunities in biomolecular science, including in drug design and development, synthetic biology, biotechnology and biocatalysis. Much biomolecular simulation demands HEC 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 work to develop 'multiscale' modelling and simulation methods to tackle these large problems, in areas such as drug metabolism and transport.

理查德·费曼（Richard Feynman）挑衅地说：“从原子的吉格林和摇摆原子的摇摆和摇摆来理解的一切都可以理解。”但是，我们如何“看到”这种摆动和摇摆不定的，并了解它如何驱动生物学呢？对生物大分子的计算机模拟越来越多地有助于应对这一挑战。实验可以提供生物大分子（例如蛋白质）的详细结构，但是很难直接研究单个分子的结构如何在短时标准的功能上变化。同样，仅单独通过实验直接研究快速过程的分子机制，例如酶中化学反应或通过膜传输的离子转运。基于基本物理学的仿真提供了填充这些关键的“差距”的潜力，对蛋白质和其他生物分子如何移动，波动，相互作用，反应，反应和功能。基于物理学的模拟补充实验在对生物学的分子理解中建立分子水平的理解：他们可以在相互作用的互动水平上测试和分析实验性数据。已经开发了多种模拟技术，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的价值，可以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。它们可以帮助设计药物和催化剂，并了解疾病的分子基础。模拟在开发生物分子科学核心的核心核心方面发挥了关键作用，即，理解生物分子的移动和弯曲的方式是其功能的核心，这是Feynman主张的真实性，证明了Feynman的真实性。从化学物理学和计算科学开发的生物素质学和计算机科学方面，包括生物素质的新机会，包括生物素养的新机会，包括生物素质的发展，包括生物素质的发展，综合，综合，综合，综合，综合，综合，综合性，综合综合性，综合性，综合性，综合性，综合性，综合性，综合性的方法。生物催化。许多生物分子模拟需要HEC资源：例如大规模的生物机器模拟，例如核糖体，质子泵和电动机，膜受体复合物，甚至整个病毒。一个特殊的挑战是跨长度和时间表的仿真集成：不同类型的问题需要不同类型的仿真方法）。我们努力开发“多尺度”建模和仿真方法，以解决这些大问题，例如药物代谢和运输等领域。