Estimating Metabolic Equilibrium Constants: Progress and Future Challenges

Reaction equilibrium constants (Keqs) are key parameters that impose thermodynamic constraints on the function of a metabolic network. An important approach for Keq estimation is the group contribution method, which utilizes chemical moiety-based estimates of compound formation energies. In this Opinion, we delineate a number of current challenges with the group contribution method, specifically: 1) problems related to the completeness and quality of data necessary for reliable estimation, and 2) inadequacies of the method to represent the physical properties of compounds.

We then highlight a number of promising approaches to deal with the limitations of group contribution methods Further advancements should lead to more accurate prediction of equilibrium constants and a better representation of cellular function under biophysical constraints.