Effect of the N3 residue on the stability of the α-helix

Teuku M. Iqbalsyah, Andrew J. Doig

    Research output: Contribution to journalArticlepeer-review


    N3 is the third position from the N terminus in the α-helix with helical backbone dihedral angles. All 20 amino acids have been placed in the N3 position of a synthetic helical peptide (CH3CO-[AAX AAAAKAAAAKAGY]-NH2) and the helix content measured by circular dichroism spectroscopy at 273 K. The dependence of peptide helicity on N3 residue identity has been used to determine a free energy scale by analysis with a modified Lifson-Roig helix coil theory that includes a parameter for the N3 energy (n3). The most stabilizing residues at N3 in rank order are Ala, Glu, Met/Ile, Leu, Lys, Ser, Gln, Thr, Tyr, Phe, Asp, His, and Trp. Free energies for the most destabilizing residues (Cys, Gly, Asn, Arg, and Pro) could not be fitted. The results correlate with N1, N2, and helix interior energies and not at all with N-cap preferences. This completes our work on studying the structural and energetic preferences of the amino acids for the N-terminal positions of the α-helix. These results can be used to rationally modify protein stability, help design helices, and improve prediction of helix location and stability.
    Original languageEnglish
    Pages (from-to)32-39
    Number of pages7
    JournalProtein science
    Issue number1
    Publication statusPublished - Jan 2004


    • α-helix
    • Circular dichroism
    • Helix propensities
    • Helix-coil theory
    • Macrodipole
    • N3 position
    • Protein folding
    • Protein stability


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