Computational Discovery of New HDAC2 Inhibitors by High Throughput Virtual Screening, Molecular Docking, MM-GBSA, and Molecular Dynamic Simulation

Abstract

The research is currently centered on investigating how FDA approved medications can be used as blockers for HDAC2. The study was started by gathering more than 4,000 drugs that have been approved by the FDA from the DrugBank database. These compounds were virtually screened to find inhibitors for HDAC2. After that the molecules were analyzed for molecular docking and those, with acceptable docking scores were underwent energy calculations using a molecular mechanics with generalized Born and surface area solvation (MM-GBSA) method. Compounds that showed decent results have been chosen for the molecular dynamic simulation studies to validate their binding affinity. Various parameters such as RMSD, RMSF, and protein ligand contacts were analyzed over a 25 ns simulation period. Encouraged by the results from the docking investigation and MM GBSA analysis two complexes vilazodone-HDAC2 and atenolol-HDAC2 were chosen for a 25 ns Desmond Schrodinger simulation of molecular dynamics (MD). The simulations showcased the stability of the receptor ligand interactions throughout the course of MD simulation.