Intrahelical side chain interactions in alpha-helices: poor correlation between energetics and frequency.

Polypeptide sequences in proteins may increase their tendency to adopt helical conformations in several ways. One is the recruiting of amino acid residues with high helical propensity. Another is the appropriate distribution of residues along the helix to establish stabilising side chain interactions. The first strategy is known to be followed by natural proteins because amino acids with high helical propensity are more frequent in alpha-helices. If proteins also followed the second strategy, stabilising amino acid pairs should be more frequent than others. To test this possibility we compared empirical energies of side chain interactions in alpha-helices with statistical energies calculated from a data base of proteins with low homology. We find some correlation between the stability afforded by the pairs and their relative abundance in alpha-helices but the realisation of energetic preferences into statistical preferences is very low. This indicates that natural alpha-helices do not regularly use intrahelical side chain interactions to increase their stability.