SIMULATION OF SUPEROXIDE SUPEROXIDE-DISMUTASE ASSOCIATION RATE FOR 6 NATURAL VARIANTS - COMPARISON WITH THE EXPERIMENTAL CATALYTIC RATE

A Brownian dynamics simulation method has been implemented to study th e superoxide-superoxide dismutase association reaction. Electrostatic potential and forces are calculated solving the linearized finite diff erence Poisson-Boltzmann equation. The accuracy of the algorithm has b een tested carrying out simulations at different ionic strength values on bovine Cu,Zn superoxide dismutase (SOD), whose three-dimensional s tructure is known at 2 Angstrom resolution, and comparing the calculat ed association rates with the experimentally determined catalytic rate s. Application of the algorithm to six Cu,Zn SOD variants shows that s imulations well reproduce the experimental catalytic rate and demonstr ates that the diffusion of the superoxide anion to the active site cop per is the rate-Limiting step in the catalytic process of Cu,Zn supero xide dismutase.