Design of helix ends

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Abstract
The amino acid sequence and chemical interactions at the ends of 163 helices were surveyed so as better to understand amino acid preferences previously observed [Richardson, J.S. & Richardson, D.C. (1988) Science240, 1648–1652]. Amino acid preferences differed from the previous survey in some significant details and in ways that might affect the choice of amino acids during the design of a protein helix. The following major conclusions about helix ends were deduced from additional patterns of amino acid occurrence and interactions that were observed. (1) A specific pair of hydrogen bonds is often observed between a glutamic acid (or glutamine) side chain at the N3 position and the N‐cap amide hydrogen, and between the N‐cap side chain (often threonine) and the N3 amide hydrogen. This reciprocal interaction may be an important means of stabilizing the N‐terminal end of a helix. (2) Negatively charged amino acids (aspartic acid and glutamic acid) at the N‐terminal end of helices may be more important in stabilizing protein helices than positively charged residues (chiefly lysine) at the C‐terminal end. (3) The identity of the residue at the N‐cap position is correlated with the backbone conformation at that position. (4) Aspartic acid (or asparagine) at the N2 or N3 position may adopt a conformation that suggests a hydrogen‐bonding interaction with the end of the helix, especially when the N‐cap side chain does not form a hydrogen bond with the end of the helix.