用于在活化动力学模拟中高效建模大分子静电和溶剂化环境的变分静电投影（VEP）方法。

Variational electrostatic projection (VEP) methods for efficient modeling of the macromolecular electrostatic and solvation environment in activated dynamics simulations.

作者信息

Gregersen Brent A, York Darrin M

机构信息

Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455-0431, USA.

出版信息

J Phys Chem B. 2005 Jan 13;109(1):536-56. doi: 10.1021/jp0469968.

DOI:10.1021/jp0469968

PMID:16851046

Abstract

New methods for the calculation of electrostatic interactions between the active dynamical region and surrounding external solvated macromolecular environment in hybrid quantum mechanical/molecular mechanical (QM/MM) simulations are presented. The variational electrostatic projection (VEP) method, and related variational reverse-mapping procedure (VEP-RVM) utilize an expansion in Gaussian surface elements for representation of electrostatic interactions. The use of a discretized surface that surrounds the active dynamical region greatly reduces the number of interactions with the particles of the external environment. The methods are tested on two catalytic RNA systems: the hammerhead and the hairpin ribozymes. It is shown that with surface elements numbering from 302 to 1202 points the direct VEP and VEP-RVM methods are able to obtain relative force errors in the range of 0.5-0.05% and 0.09-0.0001%, respectively, using a 4.0 A projection buffer. These results are encouraging and provide an essential step in the development of new variational macromolecular solvent-boundary methods for QM/MM calculations of enzyme reactions.

摘要

本文提出了在混合量子力学/分子力学（QM/MM）模拟中计算活性动力学区域与周围外部溶剂化大分子环境之间静电相互作用的新方法。变分静电投影（VEP）方法及相关的变分反向映射程序（VEP-RVM）利用高斯曲面元展开来表示静电相互作用。围绕活性动力学区域使用离散表面极大地减少了与外部环境粒子的相互作用数量。这些方法在两个催化RNA系统上进行了测试：锤头状核酶和发夹状核酶。结果表明，使用302至1202个点的表面元，直接VEP和VEP-RVM方法在使用4.0 Å投影缓冲区时，能够分别获得范围为0.5 - 0.05%和0.09 - 0.0001%的相对力误差。这些结果令人鼓舞，并为开发用于酶反应QM/MM计算的新变分大分子溶剂边界方法迈出了重要一步。