PROTEIN STRUCTURE 



C includes terms which allow for these three effects ; C is negative 

 for hydrogen-bonded configurations in both aqueous and non- 

 aqueous solvents at room temperature. There will therefore be a 

 critical chain length below which the helical configuration is un- 

 stable. This critical size has been estimated as probably between 

 8 and 15 peptide residues for a polypeptide chain in aqueous 

 solution, but this calculation neglects side-chain interactions. 

 The critical size is reduced by interchain covalent bonding ; thus 

 cystine linkages between coiled chains can be shown to contribute 

 very markedly to the stability of any array of intrinsically un- 

 stable coiled chain units (see the discussion on insulin later). 



The entropy changes which occur when water molecules 

 are bound to the — C=0 and — N — H groups, as the helix is 

 unfolded, have not been treated by Schellman. Allowance for 

 these effects would probably somewhat decrease the calculated 

 critical size for helix formation, but would not alter Schellman's 

 principal conclusions. 



Schellman has also considered the effects of electrostatic and 

 other interactions between adjacent residues. A series of adjacent 

 side chains with charges of the same sign gives rise to repulsive 

 interactions, which favor extended configurations ; if the adjacent 

 charges are of opposite sign, if hydrogen bond formation occurs 

 between adjacent side chains, or if a series of adjacent nonpolar 

 side chains is present compact configurations such as the a-helix 

 are favored. 



When an a-helix structure is broken by making an abrupt 

 alteration in the helical axis direction, stabilizing hydrogen 

 bonds are broken but little configurational entropy is gained. 

 "Broken" helices of this kind are therefore unlikely to occur. 

 This would suggest that one of the two alternatives proposed on 

 page 410 for hemoglobin — the zigzag arrangement of consecutive 

 regions of a-helix about some common axis — is the less likely 

 solution of the observed experimental discrepancies. A further 

 criticism of the zigzag arrangement is the difficulty, except 

 where the angle between the two segments is large, in forming 

 reasonably strong hydrogen bonds between free C=0 or NH 

 groups and water molecules. 



417 



