Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/22008
Título: | Selective flexibility of side-chain residues improves VEGFR-2 docking score using autodock vina |
Autor(es): | Abreu, Rui M. V. Froufe, Hugo J. C. Queiroz, Maria João R. P. Ferreira, Isabel C. F. R. |
Palavras-chave: | Drug design Virtual screening Aa residues flexibility VEGFR-2 aa residue flexibility docking |
Data: | 2012 |
Editora: | John Wiley and Sons |
Revista: | Chemical Biology & Drug Design |
Resumo(s): | Selective side-chain residue flexibility is an option available on AutoDock Vina docking software. This approach is promising as it attempts to provide a more realistic ligand-protein interaction environment, without an unmanageable increase in computer processing time. However, studies validating this approach are still scarce. VEGFR-2 (vascular endothelial growth factor receptor 2), a known protein target for anti-angiogenic agents, was used in this study. Four residues present in the VEGFR-2 kinase site were selected and made flexible: Lys866, Glu885, Cys917 and Asp1044. The docking scores for all possible combinations of flexible residues were compared to the docking scores using a rigid conformation. The best overall docking scores were obtained using the Glu883 flexible conformation, with pearson and spearman rank correlation values of 0.568 and 0.543, respectively, and a 51% increase in computer processing time. Using different VEGFR-2 X-ray structures a similar trend was observed with Glu885 flexible conformation presenting the best scores. This study demonstrates that careful use of selective side-chain residue flexibility can improve AutoDock Vina docking score accuracy, without a significant increase in computer processing time. This methodology proved to be a valuable tool in drug design when using VEGFR-2 but will also probably be useful if applied to other protein targets. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/22008 |
DOI: | 10.1111/j.1747-0285.2011.01313.x |
ISSN: | 1747-0277 |
Versão da editora: | www.wiley.com |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CDQuim - Artigos (Papers) |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
CBDD-revised2012.pdf | Documento principal aceite e revisto para publicação | 289,18 kB | Adobe PDF | Ver/Abrir |