Treatment of Halogen Bonding in the OPLS-AA Force Field: Application to Potent Anti-HIV Agents

被引：225

作者：

Jorgensen, William L. ^{[1
]}

Schyman, Patric ^{[1
]}

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

来源：

JOURNAL OF CHEMICAL THEORY AND COMPUTATION | 2012年 / 8卷 / 10期

基金：

美国国家卫生研究院;

关键词：

WATER; COMPLEXES; MODEL; HYDRATION; ATOMS;

D O I：

10.1021/ct300180w

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

The representation of chlorine, bromine, and iodine in aryl halides has been modified in the OPLS-AA and OPLS/CM1A force fields in order to incorporate halogen bonding. The enhanced force fields, OPLS-AAx and OPLS/CM1Ax, have been tested in calculations on gas-phase complexes of halobenzenes with Lewis bases, and for free energies of hydration, densities, and heats of vaporization of halobenzenes. Comparisons with results of MP2/aug-cc-pVDZ(-PP) calculations for the complexes are included. Implementation in the MCPRO software also allowed computation of relative free energies of binding for a series of HIV reverse transcriptase inhibitors via Monte Carlo/free-energy perturbation calculations. The results support the notion that the activity of an unusually potent chloro analog likely benefits from halogen bonding with the carbonyl group of a proline residue.

引用

页码：3895 / 3901

页数：7

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