FORCES BETWEEN PROTEIN MOLECULES IN SOLUTION 63 



matic reactions. If it is supposed that the catalytic site of the enzyme is situ- 

 ated at the center of a constellation of vicinal basic groups, and if there is a 

 substantial increase in dipole moment in the activation of the catalytic site- 

 substrate complex to its transition state, interaction by the fluctuation mech- 

 anism between the basic groups and their attached protons with the dipole 

 moment of the activated complex, can substantially diminish the free energy 

 of activation, in a predictable manner dependent upon pH. One of the inter- 

 esting features of this interaction is that it passes through a maximum at a 

 pH equal to the pK of the conjugate acids of the participating basic groups. A 

 consistent analysis of the pH dependence of the rates of hydrolysis of esters 

 and amides by a group of representative enzymes has been achieved by the 

 theory. 



It seems reasonable to predict that the role of the fluctuation force will turn 

 out to be important and, in certain instances, decisive in many other examples 

 of interaction between protein molecules in solution. It is clear that highly spe- 

 cific interactions might well arise from the fluctuation mechanism if the con- 

 cept of complementary patterns is invoked. In favorable orientations, steric 

 matching of a constellation on the other could well produce a redistribution of 

 protons leading to a strong specific interaction depending upon the local struc- 

 tural details of the complementary constellations. Considerations relating to 

 the specificity of the fluctuation force, as in the case of other types of interac- 

 tion, must necessarily remain speculative until more detailed knowledge of the 

 fine structure of proteins is available. 



References 



Kirkwood, J. G. 1955. The Physical Chemistry of Enzymes. General Discussion of 

 the Faraday Society, No. 20, p. 78. Aberdeen University Press, Ltd. 



Kirkwood, J. g' and J.'b. Shumaker. 1952. Proc. Nat. Acad. Sci. 38: 863. 



Timasheff, S. N., H. M. Dintzis, J. G. Kirkwood and B. D. Coleman. 1955. Proc. 

 Nat. Acad. Sci. 41: 710. 



