Decoding molecular recognition of inhibitors targeting HDAC2 via molecular dynamics simulations and configurational entropy estimation.

ABSTRACT: Molecular recognition by enzymes is a complicated process involving thermodynamic energies governing protein-ligand interactions. In order to aid the estimation of inhibitory activity of compounds targeting an enzyme, several computational methods can be employed to dissect this intermolecular contact. Herein, we report a structural dynamics investigation of an epigenetic enzyme HDAC2 in differentiating its binding to various inhibitors within the sub-sites of its active site. Molecular dynamics (MD) simulation was employed to elucidate the intermolecular interactions as well as the dynamics behavior of ligand binding. MD trajectories of five distinct HDAC2-inhibitor complexes reveal that compounds lacking adequate contacts with the opening rim of the active site possess high fluctuation a

SUBMITTER: Tateing S 

PROVIDER: S-EPMC9387782 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature