STOCHASTIC SIMULATION OF LIGAND-RECEPTOR INTERACTION

We have developed an algorithm for the stochastic simulation of ligand -receptor interactions based on 10(4)-10(5) fictitious binding sites. Reversible receptor binding was simulated by alternate random selectio n of sites, the first selection resulting in ''occupation'' if the sel ected site was ''free,'' the second selection resulting in ''dissociat ion'' if the selected site was ''occupied.'' We show that the mathemat ical formalism of mass action kinetics is predicted on purely statisti cal grounds. The model was extended by the introduction of two further selections, simulating a conformational change in the ligand-receptor complex (''receptor isomerization model''). All random selections wer e gauged separately by ''probability barriers,'' taking the place of m acroscopic kinetic rate constants. Simulation of gradual increases and gradual decreases of the fraction of occupied fictitious binding site s in the receptor isomerization model, using various combinations of ' 'rate constants,'' resulted in biexponential time dependencies, in agr eement with predictions from the integrated rate equations. Stochastic simulation of molecular processes is a powerful and versatile techniq ue, providing the researcher with a means of studying mechanisms of in creasing complexity. (C) 1997 Academic Press.