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A Multistep docking and scoring protocol for congeneric series: Implementation on kinase DFG-out type II inhibitors

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AIM: Rescoring of docking-binding poses can significantly improve molecular docking results. Our aim was to evaluate postprocessing docking protocols in order to determine the most suitable methodology for the study of the binding of congeneric compounds to protein kinases. MATERIALS & METHODS: Diverse ligand-receptor poses generated after docking were submitted to different relaxation protocols. The Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area approach was applied for the evaluation of the binding affinity of complexes obtained. The performance of various Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area methodologies was compared. RESULTS: The inclusion of a postprocessing protocol after docking enhances the quality of the results, although the best methodology is system dependent. CONCLUSION: An examination of the interactions established has allowed us to suggest useful modifications for the design of new type II inhibitors.

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GRANADINO ROLDÁN, José m., GARZÓN, Andrés, GÓMEZ GUTIÉRREZ, Patrícia, PASAMONTES FUNES, Ignacio, TOMÁS BELENGUER, Maria santos, RUBIO MARTÍNEZ, Jaime. A Multistep docking and scoring protocol for congeneric series: Implementation on kinase DFG-out type II inhibitors. _Future Medicinal Chemistry_. 2018. Vol. 10, núm. 297-318. [consulta: 27 de gener de 2026]. ISSN: 1756-8919. [Disponible a: https://hdl.handle.net/2445/135006]

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