COLLISIONS AND ENCOUNTERS IN SIMULATIONS OF RECEPTOR GTP-BINDING PROTEIN INTERACTIONS VIA SIMPLE DIFFUSION

In two intact cell systems in which GTP-binding protein (G) activity i s initiated by the presence of agonist-bound receptors (R), it has bee n demonstrated that the rate of G activation is influenced by the rate of turnover of agonist occupancy among the receptor population. G act ivity is reduced when a low concentration of agonist-occupied receptor s comprised by low fractional occupancy of a large receptor population is replaced by the presence of the same concentration of 100%-occupie d receptors. This effect has been proposed to be due to a time interva l of interaction between R and G (an encounter) that is long compared to the time of a single collision between R and G and long compared to the lifetime of an agonist-receptor complex. In a recent simulation s tudy of R-G interaction via diffusion, the effect of agonist occupancy turnover was observed but it was assumed that long encounters were no t operative. In this study, encounter intervals in simulations of R-G interaction by simple diffusion were measured in order to address that difference. The results demonstrate that relatively long encounters c omprised of multiple, separate collisions are an inherent part of R-G interaction as modelled by diffusion. The implications for further imp lementation of simulation studies of R-G interaction are discussed.