title: Molecular Dynamics Simulation of Iminosugar Inhibitor-Glycosidase Complex:  Insight into the Binding Mechanism of 1-Deoxynojirimycin and Isofagomine toward β-Glucosidase.
abstract: The binding mechanism of iminosugar inhibitor 1-deoxynojirimycin and isofagomine toward β-glucosidase was studied with nanosecond time scale molecular dynamics. Four different systems were analyzed according to the different protonated states of inhibitor and enzyme (acid/base carboxyl group, Glu166). The simulations gained quite a reasonable result according to the thermodynamic experimental fact. Further conclusions were made including the following:  (1) 1-deoxynojirimycin binds with the β-glucosidase as conjugate acid forms; (2) the slow onset inhibition of isofagomine aims to slow deprotonation of the acid/base carboxyl group which is caused by a nearly zero hydrogen bond interaction between the hydroxyls of the acid/base carboxyl group; and (3) the nucleophile carboxyl group plays an important role when the inhibitor binds with glucosidase.
authors.affiliation: Department of Computer Chemistry and Cheminformatics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, 200032, Shanghai, China, and Chemical and Pharmaceutical Institute, East China University of Science and Technology, 130 Meilong Lu, 200237, Shanghai, China.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Zhou
authors.affiliation: Department of Computer Chemistry and Cheminformatics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, 200032, Shanghai, China, and Chemical and Pharmaceutical Institute, East China University of Science and Technology, 130 Meilong Lu, 200237, Shanghai, China.
authors.forename: Jun-Hong
authors.initials: JH
authors.lastname: Zhou
authors.affiliation: Department of Computer Chemistry and Cheminformatics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, 200032, Shanghai, China, and Chemical and Pharmaceutical Institute, East China University of Science and Technology, 130 Meilong Lu, 200237, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Computer Chemistry and Cheminformatics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, 200032, Shanghai, China, and Chemical and Pharmaceutical Institute, East China University of Science and Technology, 130 Meilong Lu, 200237, Shanghai, China.
authors.forename: Min-Bo
authors.initials: MB
authors.lastname: Chen