Our present simulation showed that an excess amount of the receptors was not required for signal activation when the dissociation constant (Kd) of the ligand-receptor complex (LR) was low (10-9 or less). However, a low Kd value caused delayed LR dissociation after clearance of ligand from the extracellular space; no signal shutdown took place. These data indicate that an excess amount of receptors with high Kd (10-8 or more) was required for prompt signal propagation at physiological ligand concentrations and rapid signal cessation following ligand clearance.

Our simulations were conducted using a conventional personal computer with a CPU running at 2.6 GHz under Windows XP or 2000 operating systems, and single simulation runs typically took less than two hours. Our simulation program could be readily implemented for kinetic analysis of any signal transduction system with various parameters, and could be used by any investigator because special computing hardware and training are not required.