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

生命的一个决定性特征是运动，而正是蛋白质等生物分子移动和改变形状的能力--起着‘分子机器’的作用--支撑着这一点。大多数在原子尺度上研究生物分子的实验方法--例如X射线结晶学和核磁共振光谱学--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，这些模拟需要巨大的计算机能力。直到最近，人们还只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赫克托有能力将其增加到微秒(百万分之一秒)的时间刻度。这听起来仍然是一段很小的时间，但实际上在一微秒内就可以发生许多重要的生物过程。这个项目将研究小鼠的一种小蛋白的动力学，这种小蛋白充当分子海绵，吸收小鼠信息素的分子。这听起来可能相当深奥，但实际上是一个成熟的‘试验台系统’，用于了解药物与其靶标结合等重要过程，因此将为药物设计和开发提供非常有用的信息。

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.