title: Molecular modeling and 3D-QSAR studies on the interaction mechanism of tripeptidyl thrombin inhibitors with human alpha-thrombin.
abstract: The mechanism of inhibition of peptidyl inhibitors with thrombin was studied using molecular modeling, molecular mechanics, and CoMFA statistical analysis. A new procedure for the elucidation of binding conformations, BCSPL, is described and was employed to obtain the binding conformers of a series of 18 tripeptidyl thrombin inhibitors. Energetic studies and QSAR analysis of the BCSPL-derived conformers indicated a modest correlation between the calculated binding energies of the title compounds and their inhibitory activities to human alpha-thrombin. CoMFA analysis of the BCSPL alignment resulted in a satisfactory model of the thrombin active site.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Ji
mesh_terms: D000991:Antithrombins / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002151:Calorimetry; D003196:Computer Graphics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D000991:Antithrombins; D009842:Oligopeptides; D013917:Thrombin