膜脂-膜蛋白相互作用研究：模式动力学模拟方法

Memberane proteins play important roles in many key cellular processes. However, until asscoated with suitable lipid-bilayers these proteins might not be able to perform their desired functions. Although nowadays more and more high-resolution membrane protein structures are solved, the structure and dynamics of protein-lipid bilaryer complexes still remains poorly understood due to the lacking of atomic structure data of the complexes. This situation makes molecular dynamics (MD) simulation as one of best choice for the study of protein-lipid interactions.Unfortranetly,conventional MD simulations usually build a large number (tens of thousands to millions) of atoms for most protein-lipid systems,thus limits its implementation in most experimental and computational labs. Here we present a project to develop a normal-mode driven dynamics simulation of large protein-lipid systems.Based on our recent successful works on atomic simulation of super-large biostructures, we are exploring a divide-and-conquer strategy and the mode-synthesis method, so as to build a multi-scaled simuation program for studying protein-lipid interactions. In this project, we will try to present a user-friendly simulator package for wet-labs to analyze the allosteric conformation changes of membrane proteins in a variety of lipid-bilayer environments. Our research might provide a good direction for further development of atomic MD simulation of super-large biomolecular complexes.

膜蛋白在细胞的许多重要的生命活动中扮演着关键的作用，而大多数膜蛋白必须要置身于适合的脂双层环境中才能发挥其正常的生物功能。虽然现在实验研究者解出了越来越多的高精度膜蛋白结构，但是目前人们还无法在原子尺度上直接观测膜脂-膜蛋白超分子体系的分子结构，这就使得利用机模拟技术来研究其微观结构及动力学原理成为膜蛋白研究的一个热点。不幸的是，一般膜脂-膜蛋白系统都比较大，相应的计算工作往往需要耗费大量计算机资源而不能得到普遍应用。为此，本项目拟在我们近期关于超大分子体系动力学模拟工作基础上，利用分而治之的思想和模式合成的工具，为膜脂-膜蛋白体系的开发一个基于模式运动分析的多尺度的动力学模拟方法。我们将为膜蛋白实验组提供一套可以运行于普通工作站的研究膜蛋白在脂双层环境下的构象变化的自动模拟系统。我们的研究还可能对如何模拟一般的对超大生物分子体系动力学提供借鉴意义。