INTERMOLECULAR INTERACTION BETWEEN BOVINE PANCREATIC TRYPSIN-INHIBITOR MOLECULES PROBED BY BROWNIAN DYNAMICS SIMULATION

In this work, the bimolecular reaction kinetics of the disproportionation of disulfide groups located on the surface of bovine pancreatic trypsin inhibitor (BPTI) are analyzed by Brownian dynamics simulation. A number of increasingly realistic models are considered which account more accurately for the charge distribution of the protein as well as its detailed topography, and the results are compared with experimental results obtained by Sommer et al. (J. Mol. Biol. 1982, 159, 721). The simulations tend to overestimate the rate dependence as a function of ionic strength. This is attributed to charge complementarity since the more realistic models with a large number of charges and/or more realistic topography are in better agreement with experiment. The most realistic model considered reproduces quite accurately the experimental rates. Two approximations are made in the present study: (1) use of the test charge method to approximate the electostatic forces and (2) neglect of internal motions. In the present application, these approximations are expected to partially offset each other.