BROWNIAN DYNAMICS SIMULATIONS OF DIFFUSIONAL ENCOUNTERS BETWEEN TRIOSE PHOSPHATE ISOMERASE AND GLYCERALDEHYDE PHOSPHATE - ELECTROSTATIC STEERING OF GLYCERALDEHYDE PHOSPHATE

Brownian dynamics simulations of the diffusional encounter between the glycolytic enzyme triose phosphate isomerase (TIM) and its substrate, D-glyceraldehyde phosphate (GAP), were performed. GAP was modeled hydrodynamically as two touching spheres (a ''dumbbell'') using charges which reproduced the molecular dipole moment of the glyceraldehyde phosphate molecule as estimated by an ab initio molecular orbital calculation. The crystal structure of TIM was used to construct a detailed topographical and electrostatic grid on which the diffusion of the dumbbell was numerically simulated. By determining the number of diffusional encounters which resulted in GAP descending into the active sites of TIM with the appropriate orientation, the diffusion-controlled rate constant for the reaction was estimated to be 1.7 X 10(8) M-1 s-1. This is in reasonable agreement with the experimentally determined diffusion-controlled rate constant of 4.8 X 10(8) M-1 s-1. By reversing the direction of the dipole moment on the GAP model, it was shown that the orientational steering of the substrate by electrostatic torques can significantly increase the reaction rate constant. This effect is in addition to the previously established translational steering of the charged substrate by electrostatic forces.