A Computational Study of the Protein-Ligand Interactions in CDK2 Inhibitors: Using Quantum Mechanics/Molecular Mechanics Interaction Energy as a Predictor of the Biological Activity

dc.creatorAlzate Morales, Jans Humbeto
dc.creatorContreras, Renato
dc.creatorSoriano, Alejandro
dc.creatorTuñon, Iñaki
dc.creatorSilla, Estanislao
dc.date2022-01-11T22:09:20Z
dc.date2022-01-11T22:09:20Z
dc.date2007
dc.date.accessioned2023-08-28T20:48:31Z
dc.date.available2023-08-28T20:48:31Z
dc.identifierAlzate-Morales JH, Contreras R, Soriano A, Tuñon I, Silla E. A computational study of the protein-ligand interactions in CDK2 inhibitors: using quantum mechanics/molecular mechanics interaction energy as a predictor of the biological activity. Biophys J. 2007 Jan 15;92(2):430-9. doi: 10.1529/biophysj.106.091512.
dc.identifier0006-3495
dc.identifierhttp://hdl.handle.net/10495/25220
dc.identifier10.1529/biophysj.106.091512
dc.identifier1542-0086
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8484546
dc.descriptionABSTRACT: We report a combined quantum mechanics/molecular mechanics (QM/MM) study to determine the protein-ligand interaction energy between CDK2 (cyclin-dependent kinase 2) and five inhibitors with the N2 -substituted 6-cyclohexylmethoxypurine scaffold. The computational results in this work show that the QM/MM interaction energy is strongly correlated to the biological activity and can be used as a predictor, at least within a family of substrates. A detailed analysis of the protein-ligand structures obtained from molecular dynamics simulations shows specific interactions within the active site that, in some cases, have not been reported before to our knowledge. The computed interaction energy gauges the strength of protein-ligand interactions. Finally, energy decomposition and multiple regression analyses were performed to check the contribution of the electrostatic and van der Waals energies to the total interaction energy and to show the capabilities of the computational model to identify new potent inhibitors.
dc.descriptionCOL0065152
dc.format10
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherBiophysical Society
dc.publisherBIOPOLIMER
dc.publisherNueva York, Estados Unidos
dc.relationBiophys. J.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectSimulación por Computador
dc.subjectComputer Simulation
dc.subjectQuinasa 2 Dependiente de la Ciclina
dc.subjectCyclin-Dependent Kinase 2
dc.subjectDiseño de Fármacos
dc.subjectDrug Design
dc.subjectModelos Químicos
dc.subjectModels, Chemical
dc.subjectModelos Moleculares
dc.subjectModels, Molecular
dc.subjectUnión Proteica
dc.subjectProtein Binding
dc.subjectConformación Proteica
dc.subjectProtein Conformation
dc.titleA Computational Study of the Protein-Ligand Interactions in CDK2 Inhibitors: Using Quantum Mechanics/Molecular Mechanics Interaction Energy as a Predictor of the Biological Activity
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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