Theoretical considerations of the sensitivity of quantitative subunit hybridization

The theoretical basis of the quantitative subunit hybridization technique and its ability to measure evolutionary amino acid substitutions is examined. Homospecific:heterospecific enzyme ratios found after subunit reassociation depend upon K1.2, the equilibrium constant for the dissociation of the heterospecific enzyme. It is shown that if this constant is near the geometric mean of the two homospecific enzyme dissociation constants, as it should be in enzymes whose subunits pair isologously, the quantitative subunit hybridization method will not detect most changes in the subunit contact regions of homologous proteins.