Docking and 3D-QSAR Studies on Some HCV NS5b Inhibitors

Abstract

A theoretical study has been carried out to interpret and support experimental findings regarding inhibition mechanism of HCV NS5b. Twenty-five HCV NS5b inhibitors were docked by QM-Polarized Ligand Docking (QPLD) technique. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were used to derive 3D-QSAR models for the selected inhibitors. The CoMFA and CoMSIA models show good cross-validated (Q 2) and non-cross-validated (R 2) coefficients for the suggested inhibitors of 0.43, 0.98 and 0.65, 0.99, respectively. The inhibition mechanism was explored and validated. Details of the interactions between the inhibitors and HCV NS5b are given in terms of steric, electrostatic, hydrophobic, hydrogen bonding fields. Enhancing potency via substitutions at positions, which were explored based on these parameters. A good correlation was found between 3D-QSAR and docking results.