Abstract:

Human Phospholipase A2 (PLA2) plays important role in the inflammation process. Inhibition of PLA2 could represent a possible point of therapeutic intervention in inflammation disorders. The crystal structure of PLA2 has been solved by Wery et al. In order to understand the interaction between the ligand and the enzyme, a known inhibitor was docked to the crystal structure of PLA2 to form a complex. Then, PLA2 and its complex have been investigated by molecular dynamics simulation under the same conditions, using program CHARMM. On analysis of the complex model, we found an enlarged pocket with lower mobility compared to the uninhibited enzyme. The catalytic center is more flexible in complex, but the dynamic behavior of the remaining part in the enzyme is similar to that in the simulation. The analysis provides valuable information for drug design.

Key words: Phospholipase A₂, Molecular dynamics, Complex, Drug design