STOCHASTIC SIMULATION OF ACTIVATION IN THE G-PROTEIN CASCADE OF PHOTOTRANSDUCTION

Activation of the G-protein cascade underlying phototransduction has been modeled by simulating the two-dimensional diffusional interactions that occur at the rod disc membrane between the three reacting protein species, which are the activated rhodopsin (R(*)), the G-protein (G), and the effector protein (E, the phosphodiesterase, PDE). The stochastic simulations confirm the main predictions of a simplified analytical model (Lamb, T. D., and E. N. Pugh, 1992, Journal of Physiology 449:719-758), and extend that treatment to more complicated cases, where there is a finite probability of reaction or a finite time for reaction. The simulations also provide quantitative estimates of the efficiency of coupling from activated G-protein (G(*)) to activated effector (E(*)) in terms of the concentrations, lateral diffusion coefficients, and binding rate constants of the participating molecules; the efficiency of coupling from G(*) to E(*) is found to be not as high as in the previous simplified analytical theory. The findings can be extended to other G-protein cascades, provided that the physical parameters of those cascades are specified.