Shang Yi, Simmerling Carlos
Department of Chemistry, State University of New York, Stony Brook, NY, USA.
Methods Mol Biol. 2012;819:527-49. doi: 10.1007/978-1-61779-465-0_31.
Molecular dynamics (MD) is a way to computationally simulate the movement of particles and it is widely used to provide a dynamic perspective on biomolecules. Nowadays, the ever-growing computer power and the improvement in methodology further strengthen the role of MD in drug discovery. In this chapter, an overview of MD's application in drug discovery will be given first, using HIV-1 protease as an example. Then, the underlying theories of MD will be briefly outlined. The second half of this chapter will provide a practical protocol on how to simulate a soluble protein in solvent. All-atom simulation with either implicit solvent or explicit solvent will be covered. The former samples global conformational change more efficiently, and post-processing including angle/distance measurement, structural deviation measurement, Ramachandran plot, and secondary structure analysis will be introduced. The latter is more realistic/expensive and is generally used to finely examine local conformational rearrangement and water-mediated interactions. Post-processing including water density analysis will be described.
分子动力学（MD）是一种通过计算模拟粒子运动的方法，它被广泛用于从动态角度研究生物分子。如今，不断增长的计算机算力以及方法学的改进进一步强化了分子动力学在药物发现中的作用。在本章中，将首先以HIV-1蛋白酶为例，概述分子动力学在药物发现中的应用。然后，将简要概述分子动力学的基础理论。本章后半部分将提供一个关于如何在溶剂中模拟可溶性蛋白质的实用方案。将涵盖使用隐式溶剂或显式溶剂的全原子模拟。前者能更高效地采样全局构象变化，并将介绍包括角度/距离测量、结构偏差测量、拉氏图和二级结构分析在内的后处理方法。后者更贴近实际/成本更高，通常用于精细研究局部构象重排和水介导的相互作用。将描述包括水密度分析在内的后处理方法。
