PENENTUAN INHIBITOR SELEKTIF DALAM MENGHAMBAT KERJA ENZIM SIKLOOKSIGENASE-2 dan EFEK MUTASI RESIDU ASAM AMINO SECARA IN SILICO

Abstract

The development of selective inhibitors for Cyclooxygenase-2 (COX-2) enzymes is a strategic priority in molecular pharmacology to address the pathophysiology of inflammation without triggering gastrointestinal side effects. This report synthesizes research findings on the binding efficacy of four specific inhibitors—Celecoxib, Rofecoxib, Valdecoxib, and Etoricoxib—using an in-silico methodology based on AutoDock 4.0 docking algorithm. The primary finding reveals that Etoricoxib exhibits the highest selectivity with a ratio of 133, supported by molecular interactions at the methyl sulfone and pyridine groups. Residue mutation analysis identifies Tyrosine 385 (Y385) on COX-2 and Phenylalanine 518 (F518) on COX-1 as critical residues determining the dynamics of active site accessibility through catalytic volume change mechanisms. This report makes a significant contribution by validating computational methods as an accurate predictive tool for mapping ligand-receptor interactions on the COX-2 enzyme