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|Type:||Artigo de periódico|
|Title:||Molecular Modeling and Receptor-Dependent (RD) 3D-QSAR Approach to a Set of Antituberculosis Derivatives|
|Abstract:||In 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.|
Molecular dynamics simulation
|Editor:||Wiley-v C H Verlag Gmbh|
|Appears in Collections:||Unicamp - Artigos e Outros Documentos|
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