Stochastic simulation of chemical reactions with spatial resolution and single molecule detail

Methods are presented for simulating chemical reaction networks with a spatial resolution that is accurate to nearly the size scale of individual molecules. Using an intuitive picture of chemical reaction systems, each molecule is treated as a point-like particle that diffuses freely in three-dimensional space. When a pair of reactive molecules collide, such as an enzyme and its substrate, a reaction occurs and the simulated reactants are replaced by products. Achieving accurate bimolecular reaction kinetics is surprisingly difficult, requiring a careful consideration of reaction processes that are often overlooked. This includes whether the rate of a reaction is at steady-state and the probability that multiple reaction products collide with each other to yield a back reaction. Inputs to the simulation are experimental reaction rates, diffusion coefficients and the simulation time step. From these are calculated the simulation parameters, including the 'binding radius' and the 'unbinding radius', where the former defines the separation for a molecular collision and the latter is the initial separation between a pair of reaction products. Analytic solutions are presented for some simulation parameters while others are calculated using look-up tables. Capabilities of these methods are demonstrated with simulations of a simple bimolecular reaction and the Lotka–Volterra system.