SIDE CHAIN INTERACTIONS GOVERNING A-HELIX STABILITY

Alpha-Helix定位规则。我们计划用实验来确定

Rules Governing Alpha-Helix Location. We plan to determine experimentally the rules governing a-helix location in an otherwise unfolded polypeptide chain. Comparison with the X-ray structures of native proteins then will show if these rules also govern helix location in native proteins. The plan is to use chemically synthesized peptides (length 13-15 residues) to catalogue specific interactions between side chains which stabilize or destabilize an Alpha-helix in water. Recent work has shown that the C-peptide of ribonuclease A (residues 1-13, terminating in HSer-13 lactone) does show partial helix formation in water between 0 and 20 C (first observed by Brown & Klee, Biochemistry 8, 2876; 1971) and that helix stability is strongly pH-dependent, probably because the salt bridge Glu 9-...His 12+ is needed for helix stability (Bierzynski, Kim & Baldwin, Proc. Natl. Acad. Sci. USA, in press, 1982). We will use chemically synthesized peptides to test this proposed interaction and also to investigate other possible side chain interactions in the C-peptide helix (a possible salt bridge Glu 2-...Arg 10+, a possible hydrophobic interaction between the Phe-8 ring and the side chains of Ala-4, Ala-5, Ala-6, or a possible hydrophobic side chain between Phe-8 and the side chains of Lys-7 and His-12). Starting from these results as a base, we will proceed to measure the free energy of helix stabilization for other side chain interactions, by studying a series of chemically synthesized peptides, each differing from a preceding peptide in one side chain interaction.