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The Energetic and Structural Effects of Single Amino Acid Substitutions upon Capped α-Helical Peptides Containing 17 Amino Acid Residues. An ONIOM DFT/AM1 Study

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journal contribution
posted on 14.12.2005, 00:00 by Robert Wieczorek, J. J. Dannenberg
We evaluate the effect of the amino acid mutations of glycine, leucine, valine, phenylalanine, serine, and proline for the 10th alanine in the capped peptide, acetly(Ala)17NH2, upon the energies of the α-helices and β-strands using ONIOM DFT/AM1 molecular orbital calculations. The relative stabilities of the α-helix (to the β-strand) derive from the differences between the effects upon not only the helix but the strand as well. Thus, Ala → Pro significantly destabilizes both but destabilizes the α-helix more, while Ala → Gly stabilizes both but stabilizes the β-strand more. The theoretical results are discussed in the context of the known experimental reports. We suggest that the solvation of the unfolded state drives the helix/coil equilibrium in solution.