Synopsis
A theory of site-site interaction due to proton/charge fluctuations in protein molecules has been developed. It is shown that, with the proper geometric configuration of identical ionizable groups on matching sites, a specific attraction may be established.
This attractive force has a bell-shaped pH dependence and is maximal close to the pK of the groups involved. Various types of protein interactions are examined in the light of this theory.
Theory and Calculations
Interactions in protein systems may involve a number of different attractive and repulsive f0rces.l The types of bonds involved in protein associations can be classified as hydrogen and electrostatic interaction^.^ In as complicated a system as found in proteins these usually act cooperatively, and it is rare that any given interaction can be characterized in terms of a single type of bonding. The purpose of this paper is to discuss one type of electrostatic force, namely, that due to the fluctuation in charge and charge configuration as a result of the fluctuations of protons between a number of ionizable groups with similar free energies of Kirkwood and Shumake?, have shown that the charge fluctuation phenomenon involving all ionizable groups on a molecule may result in a nonspecific general attraction between two identical molecules. The presence of such a nonspecific attractive force in isoionic proteins has been verified e~perirnentally.'~-'~ This force is strongest at the isoionic point in the absence of supporting electrolyte, and is greatly attenuated by screening electr~lyte.~,'~ The concept of proton fluctuations on protein molecules has been found to be fully compatible with dielectric increment measurements on some proteins. 14-17 Furthermore, Kirkwoodls has shown that charge fluctuations between identical groups located in a specific site can account for the catalytic activity of some hydrolytic enzymes, while the general concept of charge fluctuations has been invoked to explain enzymatic activity in complex metabolic processes. l8 107 hydrophobic ioa S. N. TIMASHEFF