A model for the binding of low molecular weight inhibitors to the active site of thrombin

Autor:	M C, Allen, X L, Cockcroft, M G, Gruetter, J P, Priestle
Rok vydání:	1999
Předmět:	Models Molecular Molecular Weight Binding Sites Protein Conformation Thrombin Reproducibility of Results Ligands Antithrombins Protein Binding
Zdroj:	Journal of computer-aided molecular design. 13(6)
ISSN:	0920-654X
Popis:	This paper describes the construction, validation and application of an active site model of the serine protease thrombin. Initial use was made of medium resolution X-ray crystallographic structures of thrombin complexed with low molecular weight, non-specific inhibitors to create a computationally useable active site shell of the enzyme. Molecular mechanics methods were then applied to dock known ligands into the active site region in order to derive a model that would accurately predict binding conformations. Validation of the modelling process was achieved by comparison of the predicted enzyme-bound conformations with their known, crystallographic binding conformations. The resultant model was used extensively for predictive purposes prior to obtaining confirmatory crystal data relating to a ligand possessing a novel and unexpected binding component complexed to thrombin. The data served both to confirm the accuracy of the binding site model and to provide information for the further refinement of the model.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::7998fda4add2231597470c1aca2575b9 https://pubmed.ncbi.nlm.nih.gov/10584216 Zobrazit plný text záznamu Full text from SpringerLink