ELECTROSTATIC AND HYDRODYNAMIC ORIENTATIONAL STEERING EFFECTS IN ENZYME-SUBSTRATE ASSOCIATION

Diffusional encounters between a dumbbell model of a cleft enzyme and a dumbbell model of an elongated ligand are simulated by Brownian dyna mics. The simulations take into account electrostatic and hydrodynamic interactions between the molecules. It is shown that the primary effe ct of inclusion of hydrodynamic interactions into the simulation is an overall decrease in the rate constant. Hydrodynamic orientational eff ects are of modest size for the systems considered here. They are mani fested when changes in the rate constants for diffusional encounters f avored by hydrodynamic interactions are compared with those favored by electrostatic interactions as functions of the overall strength of el ectrostatic interactions. The electrostatic interactions modify the hy drodynamic torques by modifying the drift velocity of the substrate to ward the enzyme. We conclude that simulations referring only to electr ostatic interactions between an enzyme and its ligand may yield rate c onstants that are somewhat (e.g., 20%) too high, but provide realistic descriptions of the orientational steering effects in the enzyme-liga nd encounters.