D3Pockets: A Method and Web Server for Systematic Analysis of Protein Pocket Dynamics

被引：62

作者：

Chen, Zhaoqiang ^{[1
,2
]}

Zhang, Xinben ^{[1
]}

Peng, Cheng ^{[1
,2
]}

Wang, Jinan ^{[1
]}

Xu, Zhijian ^{[1
,2
]}

Chen, Kaixian ^{[1
,2
,3
]}

Shi, Jiye ^{[4
]}

Zhu, Weiliang ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China

[2] Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China

[3] Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Druggabil Res Marine Nat Prod, 1 Wenhai Rd, Qingdao 266237, Shandong, Peoples R China

[4] UCB Biopharma SPRL, Chemin Foriest, B-1420 Braine I Alleud, Belgium

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2019年 / 59卷 / 08期

基金：

中国国家自然科学基金;

关键词：

LIGAND-BINDING-SITES; DRUG; DRUGGABILITY; CAVITIES; PREDICTION; SURFACES; IDENTIFICATION; ALGORITHM; DISCOVERY; GEOMETRY;

D O I：

10.1021/acs.jcim.9b00332

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The intrinsic dynamic properties of the ligand-binding pockets of proteins are important for the protein function mechanism and thus are useful to drug discovery and development. Few methods are available to study the dynamic properties, such as pocket stability, continuity, and correlation. In this work, we develop a method and web server, namely, D3Pockets, for exploring the dynamic properties of the protein pocket based on either molecular dynamics (MD) simulation trajectories or conformational ensembles. Application of D3Pockets on five target proteins as examples, namely, HIV-1 protease, BACE1, L-ABP, GPX4, and GR, uncovers more information on the dynamic properties of the ligand-binding pockets, which should be helpful to understanding protein function mechanism and drug design.

引用

页码：3353 / 3358

页数：6

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