Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712-1062, USA.
J Chem Phys. 2011 Oct 21;135(15):155104. doi: 10.1063/1.3651626.
A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into "alpha helix" and "beta sheet" structures. The 5-residue polyalanine displays a substantial increase in the "beta strand" fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling.
本文提出了一种基于 Gay-Berne 势能和静电点多极展开的通用、可转移的粗粒 (CG) 框架，用于多肽模拟。溶剂效应由广义 Kirkwood 理论描述。CG 模型使用模型化合物在溶液中的全原子模拟结果进行校准。该 CG 模型不是通过匹配原子模型产生的整体有效力，而是在 CG 水平上显式表示静电、排斥-色散和溶剂化等基本分子间力。我们证明 CG 丙氨酸二肽模型能够在气相和溶液相定量再现全原子力场的构象能，包括静电和溶剂化成分。复制品交换分子动力学和 5 个和 12 个残基的聚丙氨酸的微秒动态模拟表明，CG 聚丙氨酸折叠成“α螺旋”和“β片层”结构。与 12 个残基的聚丙氨酸相比，5 个残基的聚丙氨酸中“β链”部分显著增加。详细的构象分布与最近的全原子模拟和实验报告的分布进行了比较。结果表明，本研究提出的新的粗粒化方法有可能为生物分子建模提供准确性和效率。
