Pharmacophore-Based Virtual Screening and Molecular Dynamics Simulation for Identification of a Novel DNA Gyrase B Inhibitor with Benzoxazine Acetamide Scaffold
Samia A. Elseginy, Manal M. Anwar
Abstract
values of 14.4 ± 0.2 and 12.4 ± 0.2 μM, respectively. The molecular docking of the six hits demonstrated that compounds 1, 2, 4, and 6 had suitable fitting modes inside the binding pocket. Molecular dynamics simulations were carried out for the six hits and the rmsd, rmsf, radius of gyration, and solvent accessible surface area parameters obtained from 100 ns molecular dynamics simulations for the six compounds complexed with a DNA gyrase B protein indicated that compound 4 (ZINC32858011) formed the most stable complex with DNA gyrase B. The binding free energy calculation with the MM-PBSA method suggested that the van der Waals interaction, followed by electrostatic force, played a significant role in the binding. Per-residue free binding energy decomposition showed that Ile78 contributed the most for the binding energy followed by Asn46, Asp49, Glu50, Asp73, Ile78, Pro79, Ala86, Ile90, Val120, Thr165, and Val167.