Barnoud Jonathan, Monticelli Luca
INSERM, UMR-S665, F-75015, Paris, France.
Methods Mol Biol. 2015;1215:125-49. doi: 10.1007/978-1-4939-1465-4_7.
Molecular dynamics (MD) simulations at the atomic scale are a powerful tool to study the structure and dynamics of model biological systems. However, because of their high computational cost, the time and length scales of atomistic simulations are limited. Biologically important processes, such as protein folding, ion channel gating, signal transduction, and membrane remodeling, are difficult to investigate using atomistic simulations. Coarse-graining reduces the computational cost of calculations by reducing the number of degrees of freedom in the model, allowing simulations of larger systems for longer times. In the first part of this chapter we review briefly some of the coarse-grained models available for proteins, focusing on the specific scope of each model. Then we describe in more detail the MARTINI coarse-grained force field, and we illustrate how to set up and run a simulation of a membrane protein using the Gromacs software package. We explain step-by-step the preparation of the protein and the membrane, the insertion of the protein in the membrane, the equilibration of the system, the simulation itself, and the analysis of the trajectory.
原子尺度的分子动力学（MD）模拟是研究模型生物系统结构和动力学的强大工具。然而，由于其计算成本高，原子模拟的时间和长度尺度受到限制。诸如蛋白质折叠、离子通道门控、信号转导和膜重塑等生物学上重要的过程，使用原子模拟很难进行研究。粗粒化通过减少模型中的自由度来降低计算成本，从而能够对更大的系统进行更长时间的模拟。在本章的第一部分，我们简要回顾一些可用于蛋白质的粗粒化模型，重点关注每个模型的具体适用范围。然后我们更详细地描述MARTINI粗粒化力场，并说明如何使用Gromacs软件包设置和运行膜蛋白模拟。我们逐步解释蛋白质和膜的制备、蛋白质插入膜中的过程、系统的平衡、模拟本身以及轨迹分析。
