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. 1992 Aug 15;89(16):7821–7825. doi: 10.1073/pnas.89.16.7821

The intrinsic helix-forming tendency of L-alanine.

J Vila 1, R L Williams 1, J A Grant 1, J Wójcik 1, H A Scheraga 1
PMCID: PMC49803  PMID: 1502201

Abstract

Conformational energy calculations have been carried out for three hexadecapeptides in water--namely, a copolymer with the sequence acetyl-AAAAKAAAA-KAAAAKA-amide, 3K(I), in both the charged and neutral forms; a neutral peptide with the sequence acetyl-AAQAAAAQAAAAQAAY-amide, AQY; and a 16-residue L-alanine homopolymer with acetyl and amide terminal groups. The conformational energy was a sum of the empirical conformational energy program for peptides (ECEPP/2) potential energy plus continuum hydration free energy. An empirical (JRF) parameter set was used for the hydration free energy, together with an electrostatic contribution to the solvent effect from charged lysines. The computed relatively high helix content of the most probable conformation of charged 3K(I) and the intermediate helix content of AQY agree reasonably well with experimental values. The computed very low helix content of the alanine homopolymer agrees with experiments on block copolymers and on host-guest random copolymers. The calculations suggest that the high helix content computed for 3K(I) is due to the sum of internal and hydration free energies of the lysine residues rather than to a high intrinsic helix-forming tendency of alanine. The principal component lowering the computed helix contents of AQY and the alanine copolymer relative to 3K(I) is hydration.

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Selected References

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