PROTEIN STRUCTURE 



acid sequences and consequent interchain packing. Since 

 major chain discontinuities do certainly exist in globular proteins, 

 we must conclude that some amino acid sequences inhibit the 

 formation of regular backbone chain configurations. 



Protein molecules have specific functions and present-day 

 thinking demands that structure and function be related in a 

 highly specific manner. In fibrous proteins, for example, hair, 

 horn, and muscle, the main function appears to be architectural 

 support or some specialized mechanical flexibility. The jobs 

 which globular proteins are built to do are not associated with 

 "mechanical" function of this kind. Reactive sites or groups on 

 a globular protein molecule are reactants in certain specific 

 chemical reactions: usually when the protein is in aqueous 

 solution. These sites must be accessible; they probably have a 

 complex, highly specific three-dimensional structure. Side- 

 chain group interactions may have a marked effect on the 

 stability of helical configurations as compared with a more 

 randomly coiled configuration. We might expect that in some 

 regions of strong side-chain interactions the a-helix would be 

 unstable. The presence of both helical and disordered chain 

 configurations in a globular protein molecule may be an im- 

 portant structural feature. It may provide both structural 

 flexibility and specific interatomic arrangements which cannot 

 be achieved with a continuous regular chain configuration. 



Helical configurations of peptide chains may be stable or 

 unstable, as compared with the more randomly coiled con- 

 figurations which are possible when the — C = O • • • • H — N — 

 hydrogen bonds are broken and the regular helix structure is 

 unfolded. The free energy of unfolding is of course the deter- 

 mining factor; if this is negative the helix, if it is formed at all, 

 will be unstable. A very important critical examination of the 

 whole problem has recently been given by Schellman (98) in 

 terms of the a-helix configuration. Heat is absorbed when a 



— CO NH — bond is broken. In a medium of low dielectric 



constant, incapable of hydrogen bond formation with the amide 



415 



