QSAR studies, docking and molecular dynamics simulation of a number of heterocyclic compounds including nitrogen oxide as new anti-tuberculosis agents

Objectiv: Mycobacterium tuberculosis (Mtb), is agent of tuberculosis. A series of novel N‑Oxide-Containing Heterocycles have been reported as selective Mycobacterium tuberculosis inhibitors. QSAR, Docking, and Molecular Dynamics Simulation studies were investigated. Imperialist Competitive Algorithm (ICA), Partial least squares (PLS), Principle Component Regression (PCR), Least Absolute Shrinkage, Selection Operator (LASSO), and Monte-Carlo simulation were used to create QSAR models. The molecular docking and molecular dynamics simulation were carried out on Mycobacterium tuberculosis (Mtb) strain H37Rv (PDB: 4XGQ). Atomic masses, atomic sanderson electronegativities, Ghose–Viswanadhan-Wendoloski antiinfective-like index and Ghose –Viswanadhan-Wendoloski hyptonic-like index were important in our study. The SMILES files have been used with coralsea software. The root-mean square errors of the training set, and the test set for ICA model, were 0.2970, 0.1395 respectively. The results of the Monte-Carlo method were the following: n=7, R²=0.9931, Q²=0.9857, MAE=0.039 (Training set); n=6, R²=0.9413, Q²=0.9107, MAE=0.367 (Test set). Molecules 10 and 11 were presented as the most stable ones that may be introduced for further investigations, including clinical experiments.