Steered molecular dynamics simulations of protein-ligand interactions  

作　　者：XU Yechun SHEN Jianhua LUO Xiaomin SHEN Xu CHEN Kaixian JIANG Hualiang 

机构地区：[1]Center for Drug Discovery and Design, State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Shanghai [2]Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China Center for Drug Discovery and Design, State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Shanghai [3]Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Science China Chemistry》2004年第5期355-366,共12页中国科学（化学英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Grant Nos.20102007,29725203 and 20072042);the State Key Program of Basic Research of China(Grant No.2002CB512802);the 863 Hi-Tech Program of China(Grant Nos.2002AA233011,2002AA233061,2001AA235051 and 2001AA 235041);Foundation of Shanghai Ministry of Science and Technology,and the Key Program of New Drug Research and Development from the Chinese Academy of Sciences.

摘　　要：Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dy- namics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be ac- cessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of bind- ing and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APAfrom HIV-1 reverse transcriptase.Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dynamics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be accessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of binding and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APAfrom HIV-1 reverse transcriptase.

关 键 词：MOLECULAR DYNAMICS simulation  steered MOLECULAR DYNAMICS simulation  atomic force microscope  avidin  biotin huperzine A  acetylcholinesterase  HIV-1 reverse transcriptas  NON-NUCLEOSIDE RT inhibitor. 

分 类 号：N[自然科学总论]