  A statistical mechanical theory is presented to predict the effects of
macromolecular crowding on protein association equilibria, accounting for both
excluded volume and attractive interactions between proteins and crowding
molecules. Predicted binding free energies are in excellent agreement with
simulation data over a wide range of crowder sizes and packing fraction. It is
shown that attractive interactions between proteins and crowding agents
counteract the stabilizing effects of excluded volume interactions. A critical
attraction strength, for which there is no net effect of crowding, is almost
independent of the crowder packing fraction.
