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Molecular dynamics simulations of a set of isoniazid derivatives bound to InhA, the enoyl‐acp reductase from M. tuberculosis
Author(s) -
Pasqualoto Kerly F. M.,
Ferreira Márcia M. C.,
SantosFilho Osvaldo A.,
Hopfinger Anton J.
Publication year - 2006
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.21055
Subject(s) - inha , molecular dynamics , chemistry , quantitative structure–activity relationship , protein data bank (rcsb pdb) , ligand (biochemistry) , solvation , molecular descriptor , stereochemistry , computational chemistry , isoniazid , molecule , receptor , tuberculosis , biochemistry , organic chemistry , medicine , pathology
Ligand‐receptor molecular dynamics simulations (MDS) were carried out for a set of hydrazides bound to the enoyl‐acp reductase from M. tuberculosis , InhA (PDB entry code 1zid). The hypothesized active conformations resulting from a previous receptor‐independent (RI) 4D‐QSAR analysis and related optimum model/alignment were used in this study. The molecular dynamics simulations (MDS) protocol employed 5 steps for each ligand‐receptor complex, the step size was 0.001 ps (1 fs), and the simulation temperature was 310 K, the same temperature used in the biological assay. An output trajectory file was saved every 20 simulation steps, resulting in 25,000 conformations. The hydration shell model was used to calculate the solvation energy of the lowest‐energy conformation obtained from each MDS. Structural parameters as well as binding energy contributions were considered in this analysis. The thermodynamic descriptors EL E1,4 , EL tors , EL vdW , EL el , and EL el+Hb appear to be more relevant to the biological activity. These findings can be meaningful for developing QSAR studies and for designing new antituberculosis agents. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006