The First Super-Microsecond Molecular Dynamics Simulation of a Protein-Ligand Complex: MUP/IBM

蛋白质-配体复合物的首次超微秒分子动力学模拟：MUP/IBM

• 批准号: EP/G004455/1
• 负责人: Charles Laughton
• 金额: $ 1.13万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG004455%2F1
• 关键词: First; Super; Microsecond; Molecular; Dynamics

One of the defining features of life is motion, and it is the ability of biological molecules like proteins to move and change shape - to function as 'molecular machines' - that underpins this. Most experimental methods to study biological molecules at the atomic scale - for example X-ray crystallography and NMR spectroscopy - can only provide static 'snapshots' of their structure. But starting with this information, computer simulation methods, particularly molecular dynamics simulations, allow us to visualise the dynamical motions of proteins and other biological molecules, enabling us to understand how these molecules 'work'. The problem is that these simulations require enormous amounts of computer power. Until recently, it was only possible to follow the motions of biological molecules for very short periods of time - a few billionths of a second. But the new UK supercomputer HECToR has the power to increase this to the microsecond (1 millionth of a second) timescale. This still sounds like a very small period of time, but actually within a microsecond a lot of important biological processes can occur. This project will study the dynamics of a small protein from mice that acts as a molecular sponge, soaking up molecules of the mouse's pheromones. This may sound quite esoteric but is actually a well-established 'testbed system' for understanding important processes like drugs binding to their targets, and so will provide very useful information to help with drug design and development.

生命的定义特征之一是运动，而生物分子（如蛋白质）移动和改变形状的能力-作为“分子机器”发挥作用-是这一点的基础。大多数在原子尺度上研究生物分子的实验方法-例如X射线晶体学和NMR光谱学-只能提供其结构的静态“快照”。但从这些信息开始，计算机模拟方法，特别是分子动力学模拟，使我们能够可视化蛋白质和其他生物分子的动态运动，使我们能够理解这些分子是如何“工作”的。问题是，这些模拟需要大量的计算机能力。直到最近，人们才能在很短的时间内跟踪生物分子的运动--几十亿分之一秒。但英国新的超级计算机HECToR有能力将其提高到微秒（百万分之一秒）的时间尺度。这听起来仍然是一个很小的时间段，但实际上在一微秒内可以发生许多重要的生物过程。这个项目将研究一种来自老鼠的小蛋白的动力学，这种蛋白充当分子海绵，吸收老鼠的信息素分子。这听起来可能很深奥，但实际上是一个完善的“试验平台系统”，用于了解药物与靶标结合等重要过程，因此将提供非常有用的信息，以帮助药物设计和开发。