Application of per-residue energy decomposition to identify the set of amino acids critical for in silico prediction of COX-2 inhibitory activity.

ABSTRACT: The enormous magnitude of scientific research carried out in the field of NSAIDs and cyclooxygenases (COXs) is known. They are crucial in pain management. COX-2 inhibitors have evolved over the years; from traditional NSAIDs to isoform-specific. The present study is aimed to identify a cluster of amino acids in the catalytic site whose energy contribution can better explain COX-2 inhibitory activity accurately than the binding energy of the whole protein. Initially, MD simulations (25 ns) and MM-PBSA calculations were performed for 8 diarylheterocyclic inhibitors. Per-residue energy decomposition studies were carried out to elucidate the energy contribution of each amino acid, and their correlation with COX-2 inhibitory activity was enumerated. A cluster of catalytic amino acids whose free

SUBMITTER: Chaudhary N 

PROVIDER: S-EPMC7550918 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature