A Discrete Approximation to Gibbs Free Energy of Chemical Reactions is Needed for Accurately Calculating Entropy Production in Mesoscopic Simulations

Abstract: In modeling the interior of cells by simulating a reaction-diffusion master equation over a grid of compartments, one employs the assumption that the copy numbers of various chemical species are small, discrete quantities. We show that in this case, textbook expressions for the change in Gibbs free energy accompanying a chemical reaction or diffusion between adjacent compartments become inaccurate. We derive exact expressions for these free energy changes under the assumption of discrete copy numbers and illustrate how these expressions reduce to the textbook expressions under a series of successive approximations leveraging the relative sizes of the stoichiometric coefficients and the copy numbers of the solutes and solvent. Numerical results are presented to corroborate the claim that if the copy numbers are treated as discrete quantities, then only these more exact expressions lead to correct equilibrium behavior. The newly derived expressions are critical for correctly tracking dissipation and entropy production in mesoscopic simulations based on the reaction-diffusion master equation formalism.