Simulations of Dynamical Properties of a Michaelis Complex: Porcine Pancreatic Elastase and the Hexapeptide, Thr-Pro-nVal-Leu-Tyr-Thr

Abstract

Molecular dynamic simulations (30ps) of the Michaelis complex of hexapeptide (Thr-Pro- nVal-Leu-Tyr-Thr) bound to porcine pancreatic elastase (PPE) hydrated by about 2000 water molecules have been performed using the AMBER 3.0 program package. Dynamical properties of the conformation of the active site have been examined. A comparison with previously reported simulations of native PPE shows that after the substrate is bound, the catalytically crucial H-bond between O_γ-H group of (Ser 195) and nitrogen N_ε (His 57) is more readily formed. These results show, however, that the H-bond does not adopt the most favorable conformation. The O_γ-H group of Ser 195 has a statistical preference for an attractive interaction with the O = C carbonyl (Ser 214) rather than the nitrogen N_ε (His 57).