title: Study on the active mechanism of β-secretase inhibitors by molecular simulations.
abstract: The proteolytic enzyme β-secretase (BACE-1) is one of potential drug targets for treating Alzheimers's disease. First, the reliable and accurate models of three-dimensional quantitative structure-activity relationship for the BACE-1 inhibitors were established, and the several important structural factors that mainly influence the inhibitory activity were obtained. Second, the results of molecular docking presented the binding mode between BACE-1 and its inhibitors, and molecular dynamic simulations provided the details of the receptor-ligand interactions. Furthermore, several new derivatives were designed and validated based on these theoretical analyses. Our studies revealed the binding mechanism between BACE-1 and its inhibitors, and provide some insights into the further structural modification and the design of new inhibitors with higher activity.
authors.affiliation: College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Yue Li
authors.initials: YL
authors.lastname: Tian
authors.affiliation: College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Lv
authors.affiliation: College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Jiao Jiao
authors.initials: JJ
authors.lastname: Li
authors.affiliation: College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China. Electronic address: zhaihl@163.com.
authors.forename: Hong Lin
authors.initials: HL
authors.lastname: Zhai
authors.affiliation: College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xiao Yun
authors.initials: XY
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D017076:Computer-Aided Design; D015195:Drug Design; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D008024:Ligands; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: 3D-QSAR; Binding mechanism; Molecular docking; Molecular dynamics; Proteolytic enzyme β-secretase