SUMMARY AND DISCUSSION 191 



Structural backing for these groups, to hold them in the right positions, but 

 probably not more than ten per cent of even a small enzyme, such as ribonucle- 

 ase, would be needed for this purpose. 



I suggest that large size may be needed to keep the molecules from diffusing 

 through tissues, through the pores. I agree with Dr. Anfinsen that in part large 

 size may be just an evolutionary accident. Proteins are useful because their 

 structures can be varied in many different ways, and a particular protein may 

 undergo mutation, variation — a gene undergoes mutation to change one little 

 region of a protein molecule so as to make it useful as an enzyme, and then it 

 continues to be manufactured generation after generation for this purpose. 



Professor Kirkwood: I would like to comment on the remark you made and 

 on one of the remarks which Dr. Anfinsen made. 



In regard to the role of the fluctuation force, I am emphasizing this, as I 

 said, because I am working on it at the moment, but I do not maintain that it 

 is a panacea for everything. However, I would like to disagree with you in the 

 statement that this force is only important for isoelectric proteins. 



It is true that in some experiments we were considering the contributions to 

 essentially long-range interaction between protein molecules as a whole in iso- 

 lating the pure charge fluctuation effect; that would be most important for 

 isoionic proteins. However, in the discussion of the possible role of fluctuation 

 force in the case of enzymes, one can imagine that the complementariness is 

 concerned not only with a very local fit in which essentially short-range forces 

 play a role, but that also one can have a more complicated peripheral pattern 

 that could contribute, not only to the binding of the molecule which is being 

 attached, say the substrate to an enzyme, but also to the free energy of activa- 

 tion. 



Then there is another point that I think could be brought up here. It is not 

 new, but has not been mentioned in our discussions. That has to do with the 

 role of such forces as van der Waals forces. It was touched upon obliquely by 

 Dr. Jehle when he was speaking of the bouyancy effect. When one is considering 

 van der Waals forces between parts of two protein molecules or in a protein 

 molecule, stabilizing the helical structures, I think that it is erroneous to speak 

 of these forces as direct interactions between the non-polar groups which are 

 coming into close contact, although very often this statement is made. 



If one is working in aqueous solution, the direct interaction between methyl 

 groups is virtually negligible in bringing them together in comparison with the 

 energy that is gained by making more contacts between water. That is, if you 

 bring two non-polar groups from infinity into contact, the gain is not so much 

 due to the direct van der W'aals interaction between these two groups as to the 

 fact that in making the contact between the two non-polar groups you form 

 more water contacts and gain your energy indirectly in this way. 



Therefore, I think that Dr. Wilson's estimates of van der Waals energies 



