Addition of side chain interactions to modified Lifson-Roig helix-coil theory: Application to energetics of phenylalanine-methionine interactions

B. J. Stapley, C. A. Rohl, A. J. Doig

    Research output: Contribution to journalArticlepeer-review

    Abstract

    We introduce here i, i + 3 and i, i + 4 side chain interactions into the modified Lifson-Roig helix-coil theory of Doig et al. (1994, Biochemistry 33:3396-3403). The helix/coil equilibrium is a function of initiation, propagation, capping, and side chain interaction parameters. If each of these parameters is known, the helix content of any isolated peptide can be predicted. The model considers every possible conformation of a peptide, is not limited to peptides with only a single helical segment, and has physically meaningful parameters. We apply the theory to measure the i, i + 4 interaction energies between Phe and Met side chains. Peptides with these residues spaced i, i + 4 are significantly more helical than controls where they are spaced i, i + 5. Application of the model yields ΔG for the Phe- Met orientation to be -0.75 kcal · mol-1, whereas that for the Met-Phe orientation is -0.54 kcal · mol-1. These orientational preferences can be explained, in part, by rotamer preferences for the interacting side chains. We place Phe-Met i, i + 4 at the N-terminus, the C-terminus, and in the center of the host peptide. The model quantitatively predicts the observed helix contents using a single parameter for the side chain-side chain interaction energy. This result indicates that the model works well even when the interaction is at different locations in the helix.
    Original languageEnglish
    Pages (from-to)2383-2391
    Number of pages8
    JournalProtein science
    Volume4
    Issue number11
    Publication statusPublished - 1995

    Keywords

    • α-helix
    • helix-coil
    • hydrophobic
    • protein folding
    • protein stability
    • side chain

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