Inflammation is the complex biolog ical response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Infection is caused by an exogenous pathogen, while inflammation is the response of the organism to the pathogen. Phospholipase A (EC 3.1.1.4) is a key enzyme of the cascade mechanism involved in the production of pro-inflammatory 2 compounds known as eicosanoids. The binding of Phospholipase A (PLA ) to membrane surfaces and the hydrolysis of 2 2 phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before cleavage. The PLA á-Tocopherol (á-TP) complex is the first evidence of inhibition of PLA by Vitamin E (á-TP). PLA 2 2 2 contains two homologous chains in an asymmetric unit (Chain A & B). The crystal structure of á-TP bound Viper russelli PLA 2 with resolution 1.8 ? (PDBID: 1KPM) is available in the literature [1]. The feature to be considered here is the binding of vitamin E only in chain A. The reasons for the specificity in binding with chain A is the orientation of an aromatic ring (of W31), which is present in the gateway of hydrophobic channel that forms the active site of enzyme. Another reason may be presence of three water molecules in the active site of molecule B and not in molecule A. The torsion angles (ö, ø) for the backbone of W31 in molecules A and B are -94?, -30? and -128?, 170? respectively [1]. The hypothesis assumed was that the change in conformation of binding site and the changes in Trp31 orientation are responsible for binding of ligand. The present work is focusing on molecular dynamic simulation of PLA2- a-TP complex. The resultant trajectory is probed for the evidence to prove the hypothesis.

Key words: Phospholipase A2, a-Tocopherol, Molecular Dynamics Simulation, Generalized Born Simulation, Amber.