92 I. M. KLOTZ 



y. 



^^ = ^'"intrinsic "" ^'^ elect. 



AF = AF 



intrinsic 



Fig. 1 



Now, these complexes can be rather surprisingly strong even if the protein 

 carries a very substantial negative charge and the organic molecule which we 

 are considering also carries a negative charge. In fact, the last example which 

 I shall discuss will point out that despite the fact that the protein carries a 

 negative charge, if we compare the binding of two molecules, organic molecules 

 of roughly equal size, one of which has a minus charge and the other of which 

 has a plus charge, in which case you would expect the plus-charged one to be 

 more strongly bound, cjuite the contrary happens; the negatively-charged one 

 is more strongly bound. 



That is a puzzle we may have to get to if I have time, but, for the moment, 

 let us just examine the more common case of a negative organic molecule. 

 This is perhaps a more interesting case anyway, because so many of the me- 

 tabolites in biological systems are anions and the enzymes with which they 

 interact are usually at a pH at which they, too, are anions. 



There are many ways in which one can affect the strength of this interaction 

 through the environment. For one thing, you can change the ionic environment, 

 as Professor Kirkwood mentioned, and then you will get the Debye-Huckel 

 screening effect, but I shall not go into that. You can change the charge on the 

 protein, too. One effect that I want to mention in detail, because I hope to give 

 something that we have not published yet, is the effect of the dielectric constant 



