The application of the MM/GBSA method in the binding pose prediction of FGFR inhibitors

被引：56

作者：

Chen, Yu ^{[1
,2
]}

Zheng, Yongxiang ^{[1
,2
]}

Fong, Pedro ^{[3
]}

Mao, Shengjun ^{[1
,2
]}

Wang, Qiantao ^{[1
,2
]}

机构：

[1] Sichuan Univ, West China Sch Pharm, Sichuan Engn Lab Plant Sourced Drug, Key Lab Drug Targeting & Drug Delivery Syst,Educ, Chengdu 610041, Peoples R China

[2] Sichuan Univ, West China Sch Pharm, Sichuan Res Ctr Drug Precis Ind Technol, Chengdu 610041, Peoples R China

[3] Macao Polytech Inst, Sch Hlth Sci & Sports, Rua Luis Gonzaga Gomes, Macau, Peoples R China

来源：

PHYSICAL CHEMISTRY CHEMICAL PHYSICS | 2020年 / 22卷 / 17期

基金：

中国国家自然科学基金;

关键词：

DOCKING; PERFORMANCE; ACCURACY; MM/PBSA; SITE;

D O I：

10.1039/d0cp00831a

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 success of a structure-based drug is highly dependent on a known binding pose of the protein-ligand system. However, this is not always available. In this study, we set out to explore the applicability of the popular and easy-to-use MD-based MM/GBSA method to determine the binding poses of known FGFR inhibitors. It was found that MM/GBSA combined with 100 ns of MD simulation significantly improved the success rate of docking methods from 30-40% to 70%. This work demonstrates a way that the MM/GBSA method can be more accurate than it is in ligand ranking, filling a gap in structure-based drug discovery when the binding pose is unknown.

引用

页码：9656 / 9663

页数：8

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