Molecular Docking of Ipalbidine into Human Cyclooxygenase-2 Protein Crystal Structures

Cyclooxygenase-2 (COX-2) is an enzyme responsible for the production of the prostaglandins, lipid molecules related to pain, inflammation, etc. Ipalbidine is a compound extracted from the crushed seeds isolated from Ipomea Alba L. (Moon Flower), which is a herbaceous vine usually found in tropical and subtropical areas in the world. The strength of the binding between a biomolecule and a ligand (drug or inhibitor) can be expressed in terms of binding affinity. When performing molecular docking, the binding affinity of a ligand bound to a receptor, in this case Ipalbidine bound to COX-2 structures, can be acquired. The seven currently available human COX-2 structures from the Protein Data Bank have been downloaded and prepared for molecular docking. Four programs have been used for the study: Autodock Tools, Autodock Vina, Visual Molecular Dynamics, and Chimera. After preparation, the binding affinities of the original bound ligands within the respective COX-2 structures were calculated. Next, the binding affinities of Ipalbidine and the seven crystal structures of COX-2 were acquired using molecular docking. The results show that Ipalbidine has a slightly lower binding affinity to the COX-2 structures compared to the original bound ligands, except for one. However, the rigid COX-2 crystal structures used in this study are optimized to accommodate the original bound ligands, not lpalbidine. In other words, the docking results for lpalbidine are expected to systematically underestimate binding affinities.