PNNL

Abstract

Kinetic probabilities of state are usually based on empirical measurements, while thermodynamic state probabilities are based on the assumption that chemical species are distributed to according to a multinomial Boltzmann distribution. While the use of kinetic simulations is desirable, obtaining all the mass action rate constants necessary to carry out kinetic simulations is an overwhelming challenge. Here, the kinetic probability of a state is compared in depth to the thermodynamic probability of a state for sets of coupled reactions. The entropic and energetic contributions to thermodynamic stable states are described and compared to entropic and energetic contributions of kinetic steady states. It is shown that many kinetic steady states are possible for a system of coupled reactions depending on the relative values of the mass action rate constants, but only one of these corresponds to a thermodynamically stable state. Furthermore, the thermodynamic stable state corresponds to a minimum free energy state. The use of thermodynamic simulations of state to model metabolic processes is attractive, since metabolite levels and energy requirements of pathways can be evaluated using only standard free energies of formation as parameters in the probability distribution. In chemical physics, the assumption of a Boltzmann distribution is the basis of transition state theory for modeling transitory species. Application to stable species, such as those found in metabolic processes, is a less severe assumption that would enable the use of simulations of state.