Molecular Modeling and Receptor-Dependent (RD) 3D-QSAR Approach to a Set of Antituberculosis Derivatives

dc.creatorPasqualoto, KFM
dc.creatorFerreira, MMC
dc.date2009
dc.dateDEC
dc.date2014-11-17T01:46:12Z
dc.date2015-11-26T16:35:09Z
dc.date2014-11-17T01:46:12Z
dc.date2015-11-26T16:35:09Z
dc.date.accessioned2018-03-28T23:17:32Z
dc.date.available2018-03-28T23:17:32Z
dc.identifierQsar & Combinatorial Science. Wiley-v C H Verlag Gmbh, v. 28, n. 41984, n. 1455, n. 1464, 2009.
dc.identifier1611-020X
dc.identifierWOS:000273713200023
dc.identifier10.1002/qsar.200960035
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/57795
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/57795
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/57795
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1271419
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionIn this study, receptor-dependent (RD) 3D-QSAR models were built for a set of thirty-seven isoniazid derivatives bound to the enoyl-acp reductase from M. tuberculosis, called InhA (PDB entry code Izid). Ligand-receptor (L-R) molecular dynamics (MD) simulations [500000 steps; the step size was 0.001 ps (1 fs)] were carried out at 310 K (biological assay temperature). The hypothesized active conformations resulting from a previously reported receptor independent (IR) 4D-QSAR analysis were used as the molecular geometries of each ligand in this structure-based L-R binding research. The dependent variable is the reported MIC values against M. tuberculosis var. bovis. The independent variables (descriptors) are energy terms of a modified first-generation AMBER force field combined with a hydration shell aqueous solvation model. Genetic function approximation (GFA) formalism and partial least squares (PLS) regression were employed as the fitting functions to develop 3D-QSAR models. The bound ligand solvation energy, the sum of electrostatic and hydrogen bonding energies of the unbound ligand, the bending energy of the unbound ligand, the electrostatic intermolecular L-R energy, and the change in hydrogen bonding energy upon binding were found as important energy contributions to the binding process. The 3D-QSAR model at 310 K has good internal and external predictability and may be regarded as representative of the binding process of ligands to InhA.
dc.description28
dc.description41984
dc.description1455
dc.description1464
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionChem21 Group, Inc
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageen
dc.publisherWiley-v C H Verlag Gmbh
dc.publisherWeinheim
dc.publisherAlemanha
dc.relationQsar & Combinatorial Science
dc.relationQSAR Comb. Sci.
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectMolecular modeling
dc.subjectEnoyl-ACP reductase
dc.subjectMolecular dynamics simulation
dc.subjectStructure-based design
dc.subjectTuberculosis
dc.subjectDrug design
dc.subjectFatty-acid Biosynthesis
dc.subjectMycobacterium-tuberculosis
dc.subjectIsoniazid Derivatives
dc.subjectEscherichia-coli
dc.subjectRational Design
dc.subjectForce-field
dc.subjectReductase
dc.subjectDynamics
dc.subjectNadh
dc.subjectInha
dc.titleMolecular Modeling and Receptor-Dependent (RD) 3D-QSAR Approach to a Set of Antituberculosis Derivatives
dc.typeArtículos de revistas


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