Abstract

To analyze the structural features that dictate the selectivity of the two isoforms of the cyclooxygenase (COX), the three-dimensional structure of COX-1/COX-2 was assessed by means of binding energy calculation by way of virtual molecular dynamic simulations using ligand sesquiterpenoid Pogostemon herba. This study was conducted to investigate the molecular interaction between ligand alphabulnesene (CID94275), alpha-guaiene (CID197152), seychellene (CID519743), and alpha-patchouli alcohol isomers (CID442384, CID521903, CID6432585, CID3080622, CID10955174, and CID56928117) to COX-1 and COX-2. Molecular docking tools proposed by Hex 8.0 were employed in this research. Discovery Studio Client 3.5 software tool and virtual molecular dynamic 1.9.1 software were also used to visualize the molecular interactions identified in this research. In order to calculate the binding energy of the molecular dynamic interaction, AMBER12 software was utilized. Results of the analysis on all sesquiterpenoid indicate that those compounds were the inhibitors of COX-1 and COX-2. Overall, the binding energy calculations (using PBSA Model Solvent) of alpha-patchouli alcohol (CID521903) and seychellene (CID519743) have been identified as the candidates of non-selective inhibitor; alpha-bulnesene (CID94275), alpha-guaiene (CID107152), and alpha-patchouli alcohol isomers (CID6432585, CID3080622, CID10955174, CID56928117) have been suggested as the candidates for a selective COX-1 inhibitor; whereas alpha-patchouli alcohol (CID442384) was the candidate for a selective COX-2 inhibitor.

Keywords: molecular dynamic, molecular docking, screening, sesquiterpenoid, sesquiterpenoid alcohol, pogostemon herba, alpha-bulnesene, alpha-guaiene, seychellene, alpha-patchouli alcohol isomers, cyclooxygenase, protein COX-1/COX-2, binding energy, scoring
