Vanommeslaeghe Kenno, Guvench Olgun, MacKerell Alexander D
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn St, HSFII Rm 633, Baltimore, MD 21201.
Curr Pharm Des. 2014;20(20):3281-92. doi: 10.2174/13816128113199990600.
Molecular Mechanics (MM) force fields are the methods of choice for protein simulations, which are essential in the study of conformational flexibility. Given the importance of protein flexibility in drug binding, MM is involved in most if not all Computational Structure-Based Drug Discovery (CSBDD) projects. This paper introduces the reader to the fundamentals of MM, with a special emphasis on how the target data used in the parametrization of force fields determine their strengths and weaknesses. Variations and recent developments such as polarizable force fields are discussed. The paper ends with a brief overview of common force fields in CSBDD.
分子力学（MM）力场是蛋白质模拟的首选方法，而蛋白质模拟在构象灵活性研究中至关重要。鉴于蛋白质灵活性在药物结合中的重要性，分子力学参与了大多数（即便不是全部）基于计算结构的药物发现（CSBDD）项目。本文向读者介绍分子力学的基本原理，特别强调力场参数化中使用的目标数据如何决定其优缺点。文中还讨论了诸如可极化力场等变体和最新进展。本文最后简要概述了CSBDD中的常见力场。
