Iwaoka Michio, Tomoda Shuji
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8902, Japan.
J Comput Chem. 2003 Jul 30;24(10):1192-200. doi: 10.1002/jcc.10259.
A simple strategy to compose a new all-atom protein force field (named as the SAAP force field), which utilizes the single amino acid potential (SAAP) functions obtained in various solvents by ab initio molecular orbital calculation applying the isodensity polarizable continuum model (IPCM), is presented. We considered that the total energy function of a protein force field (E(TOTAL)) is divided into three components; a single amino acid potential term (E(SAAP)), an interamino acid nonbonded interaction term (E(INTER)), and a miscellaneous term (E(OTHERS)), which is ignored (or considered to be constant) at the current version of the force field. The E(INTER) term consists of electrostatic interactions (E(ES')) and van der Waals interactions (E(LJ')). Despite simplicity, the SAAP force field implicitly involves the correlation among individual terms of the Lifson's potential function within a single amino acid unit and can treat solvent effects unambiguously by choosing the SAAP function in an appropriate solvent and the dielectric constant (D) of medium. Application of the SAAP force field to the Monte Carlo simulation of For-Ala(2)-NH(2) in vacuo reasonably reproduced the results of the extensive conformational search by ab initio molecular orbital calculation. In addition, the preliminary Monte Carlo simulations for For-Gly(10)-NH(2) and For-Ala(10)-NH(2) showed reversible transitions from the extended to the pseudosecondary structures in water (D = 78.39) as well as in ether (D = 4.335). The result suggested that the new approach is efficient for fast modeling of protein structures in various environments. Decomposition analysis of the total energy function (E(TOTAL)) by using the SAAP force field suggested that conformational propensities of single amino acids (i.e., the E(SAAP) term) may play definitive roles on the topologies of protein secondary structures.
提出了一种构建新的全原子蛋白质力场（命名为SAAP力场）的简单策略，该策略利用通过应用等密度极化连续介质模型（IPCM）的从头算分子轨道计算在各种溶剂中获得的单氨基酸势（SAAP）函数。我们认为蛋白质力场的总能量函数（E(TOTAL)）分为三个部分：单氨基酸势项（E(SAAP)）、氨基酸间非键相互作用项（E(INTER)）和杂项（E(OTHERS)），在当前版本的力场中杂项被忽略（或视为常数）。E(INTER)项由静电相互作用（E(ES')）和范德华相互作用（E(LJ')）组成。尽管简单，但SAAP力场在单个氨基酸单元内隐含地涉及Lifson势函数各个项之间的相关性，并且通过在适当的溶剂和介质的介电常数（D）中选择SAAP函数，可以明确处理溶剂效应。将SAAP力场应用于真空中For-Ala(2)-NH(2)的蒙特卡罗模拟，合理地再现了从头算分子轨道计算进行的广泛构象搜索的结果。此外，对For-Gly(10)-NH(2)和For-Ala(10)-NH(2)的初步蒙特卡罗模拟表明，在水（D = 78.39）以及醚（D = 4.335）中，从伸展结构到假二级结构存在可逆转变。结果表明，这种新方法对于在各种环境中快速建模蛋白质结构是有效的。使用SAAP力场对总能量函数（E(TOTAL)）进行的分解分析表明，单个氨基酸的构象倾向（即E(SAAP)项）可能在蛋白质二级结构的拓扑结构中起决定性作用。
