Biotechnologg Techniques Vol 2 No 1 23-28 (1988) Received December 17 A GROUP CONTRIBUTION METHOD FOR THE ESTIMATION OF EQUILIBRIUM CONSTANTS FOR BIOCHEMICAL REACTIONS Michael L. Mavrovouniotis, Patrick Bayol, Tu-Kien Michael Lam, George Stephanopoulos*, and Gregory Stephanopoulos Department of Chemical Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts 02139 ABSTRACT Using Gibbs Energies of compounds, as well as Gibbs Energy changes and equilibrium constants of biochemical reactions, the contributions of functional groups to the Gibbs Energy (in aqueous solution, temperature 25oc, and pH=7) have been estimated. These contributions allow the estimation of the Gibbs Free Energy and the equilibrium constant of a biochemical reaction, given the structure of the reactants and products. INTRODUCTION Values for equilibrium constants for biochemical reactions, especially in less studied pathways, are rarely found in the literature. A reaction's equilibrium constant, K, can be obtained from the corresponding Standard Gibbs Free Energy AG ~ through the relation: K = exp (-AG~ AG ~ is equal to the difference between the Standard Gibbs Free Energies of Formation of the products and the Standard Gibbs Free Energies of Formation of the reactants. For the rest of this paper, unless otherwise specified, the term "Gibbs Energy" denotes the o Standard Gibbs Free Energy of Formation of a molecule, or the Standard Gibbs Free Energy of a reaction, both in aqueous solution. Group-contribution methods (e.g., Reid et al., 1977, Joback and Reid, 1987) have been widely used to estimate thermodynamic properties for compounds. Such methods are developed by using data to estimate the contributions of different functional groups to the property of interest, so that the errors, i.e., the differences between known and predicted values, are minimized. Then, to estimate the property for a particular compound, one breaks the compound into functional groups and sums up the contributions of the groups. Group-contribution methods have focused on ideal- 23