Excluded volume as a determinant of macromolecular structure and reactivity

The effect of excluded volume on the thermodynamic activity of globular macromolecules and macromolecular complexes in solution is studied in the hard‐particle approximation. Activity coefficients are calculated as a function of the fraction of total volume occupied by macromolecules using relations obtained from scaled particle and lattice models. Significant and readily observable effects are predicted to occur as the fraction of volume occupied by globular macromolecules increases, including the following: (i) Compact quasi‐spherical macromolecular conformations become increasingly energetically favored over extended anisometric conformations. (ii) Self‐ and heteroassociation processes are enhanced, particularly those leading to the formation of compact quasi‐spherical aggregates. (iii) Depending upon the details of the reaction mechanism, the rate of an enzyme‐catalyzed reaction may monotonically decrease, go through a maximum, or exhibit more complex behavior. A given degree of volume occupancy by larger macromolecules is predicted to have less effect on the structure and self‐association of smaller macromolecules than the same degree of volume occupancy by smaller macromolecules has on the structure and self‐association of larger macromolecules.