Evaluation of the absolute affinity of neuraminidase inhibitor using steered molecular dynamics simulations

被引：14

作者：

Nguyen Minh Tam ^{[1
,2
]}

Minh Tho Nguyen ^{[3
,4
]}

Son Tung Ngo ^{[1
,2
]}

机构：

[1] Ton Duc Thang Univ, Computat Chem Res Grp, Ho Chi Minh City, Vietnam

[2] Ton Duc Thang Univ, Fac Appl Sci, Ho Chi Minh City, Vietnam

[3] ICST, Quang Trung Software City, Ho Chi Minh City, Vietnam

[4] Katholieke Univ Leuven, Dept Chem, Celestijnenlaan 200F, B-3001 Leuven, Belgium

来源：

JOURNAL OF MOLECULAR GRAPHICS & MODELLING | 2017年 / 77卷

关键词：

Fast pulling of ligand; Neuraminidase; NEMD; Absolute affinity; Interaction energy; Pulling work; BETA; 11-40; TRIMER; FREE-ENERGY; FORCE-FIELD; INFLUENZA; DRUG; PERTURBATION; ANALOGS; DESIGN; TOOL;

D O I：

10.1016/j.jmgm.2017.08.018

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The absolute free energy difference of binding (Delta G) between neuraminidase and its inhibitor was evaluated using fast pulling of ligand (FPL) method over steered molecular dynamics (SMD) simulations. The metric was computed through linear interaction approximation. Binding nature was described by free energy differences of electrostatic and van der Waals (vdW) interactions. The finding indicates that vdW metric is dominant over electrostatics in binding process. The computed values are in good agreement with experimental data with a correlation coefficient of R=0.82 and error of sigma Delta G(exp) = 2.2 kcal/mol. The results were observed using Amber99SB-ILDN force field in comparison with CHARMM27 and GROMOS96 43a1 force fields. Obtained results may stimulate the search for an Influenza therapy. (C) 2017 Elsevier Inc. All rights reserved.

引用

页码：137 / 142

页数：6

共 43 条

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