Stabilizing nonpolar/polar side-chain interactions in the α-helix

Charles D. Andrew, Simon Penel, Gareth R. Jones, Andrew J. Doig

    Research output: Contribution to journalArticlepeer-review


    A simplistic, yet often used, view of protein stability is that amino acids attract other amino acids with similar polarity, whereas nonpolar and polar side chains repel. Here we show that nonpolar/polar interactions, namely Val or Ile bonding to Lys or Arg in a-helices, can in fact be stabilizing. Residues spaced i, i + 4 in α-helices are on the same face of the helix, with potential to favorably interact and stabilize the structure. We observe that the nonpolar/polar pairs Ile-Lys, Ile-Arg, and ValLys occur in protein helices more often than expected when spaced i, i + 4. Partially helical peptides containing pairs of nonpolar/polar residues were synthesized. Controls with i, i + 5 spacing have the residues on opposite faces of the helix and are less helical than the test peptides with the i, i + 4 interactions. Experimental circular dichroism results were analyzed with helix-coil theory to calculate the free energy for the interactions. All three stabilize the helix with ΔG between -0.14 and -0.32 kcal · mol-11. The interactions are hydrophobic with contacts between Val or Ile and the alkyl groups in Arg or Lys. Side chains such as Lys and Arg can thus interact favorably with both polar and nonpolar residues. © 2001 Wiley-Liss, Inc.
    Original languageEnglish
    Pages (from-to)449-455
    Number of pages6
    JournalProteins: Structure, Function and Bioinformatics
    Issue number4
    Publication statusPublished - 1 Dec 2001


    • α-helix
    • Helix-coil
    • Hydrophobic
    • Modified Lifson-Roig theory
    • Protein folding
    • Side-chain


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