Accessing the Applicability of Polarized Protein-Specific Charge in Linear Interaction Energy Analysis

被引：7

作者：

Jia, Xiangyu ^{[1
]}

Zeng, Juan ^{[1
]}

Zhang, John Z. H. ^{[1
,2
]}

Mei, Ye ^{[1
]}

机构：

[1] E China Normal Univ, Inst Theoret & Computat Sci, Dept Phys, State Key Lab Precis Spect, Shanghai 200062, Peoples R China

[2] NYU Shanghai, NYU ECNU Ctr Computat Chem, Shanghai 200062, Peoples R China

来源：

JOURNAL OF COMPUTATIONAL CHEMISTRY | 2014年 / 35卷 / 09期

基金：

中国国家自然科学基金;

关键词：

polarization; linear interaction energy; force field; charge model; avidin; -secretase; LIGAND-BINDING AFFINITIES; VAN-DER-WAALS; MOLECULAR-DYNAMICS; BETA-SECRETASE; ATOMIC CHARGES; ELECTROSTATIC POLARIZATION; CONTINUUM ELECTROSTATICS; EFFICIENT GENERATION; SCORING FUNCTION; AM1-BCC MODEL;

D O I：

10.1002/jcc.23547

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The reliability of the linear interaction energy (LIE) depends on the atomic charge model used to delineate the Coulomb interaction between the ligand and its environment. In this work, the polarized protein-specific charge (PPC) implementing a recently proposed fitting scheme has been examined in the LIE calculations of the binding affinities for avidin and -secretase binding complexes. This charge fitting scheme, termed delta restrained electrostatic potential, bypasses the prevalent numerical difficulty of rank deficiency in electrostatic-potential-based charge fitting methods via a dual-step fitting strategy. A remarkable consistency between the predicted binding affinities and the experimental measurement has been observed. This work serves as a direct evidence of PPC's applicability in rational drug design. (c) 2014 Wiley Periodicals, Inc.

引用

页码：737 / 747

页数：11

共 79 条

[1] Applying linear interaction energy method for binding affinity calculations of podophyllotoxin analogues with tubulin using continuum solvent model and prediction of cytotoxic activity [J].