Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor

作     者：Gui-xia LIU~(2,3,4) Jin-zhi TAN~2 Chun-ying NIU~2 Jian-hua SHEN~(2,3) Xiao-min LUO~2 Xu SHEN~(2,3) Kai-xian CHEN~2 Hua-liang JIANG~(2,3,4)2 Center for Drug Discovery and Design,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 201203,China 3 School of Pharmacy,East China University of Science and Technology Shanghai 200237,China 

作者机构：Center for Drug Discovery and Design State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China School of Pharmacy East China University of Science and Technology Shanghai China 

出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))

年 卷 期：2006年第27卷第1期

页      面：100-110页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 10[医学] 

基　　金：国家973计划 国家自然科学基金 上海市科委项目 中国科学院新药研究基金 国家863计划 

主　　题：molecular dynamics simulation principal component analysis protein-tyrosine phosphatase 1B type 2 diabetes 

摘      要：Aim:To investigate the dynamic properties of protein-tyrosine phosphatase (PTP)1B and reveal the structural factors responsible for the high inhibitory potencyand selectivity of the inhibitor SNA for ***:We performed moleculardynamics (MD) simulations using a long time-scale for both PTP1B and PTP1Bcomplexed with the inhibitor SNA,the most potent and selective PTP1B inhibitorreported to *** trajectories were analyzed by using principal ***:Trajectory analyses showed that upon binding the ligand,theflexibility of the entire PTP1B molecule *** most notable change is themovement of the *** simulation results also indicated that electro-static interactions contribute more to PTP 1B-SNA complex conformation than thevan der Waals interactions,and that Lys41,Arg47,and Asp48 play important rolesin determining the conformation of the inhibitor SNA and in the potency andselectivity of the *** these,Arg47 contributed *** results werein agreement with previous experimental ***:The informationpresented here suggests that potent and selective PTP1B inhibitors can be de-signed by targeting the surface residues,for example the region containing Lys41,Arg47,and Asp48,instead of the second phosphate binding site (besides theactive phosphate binding site).