The Molten Helix: Effects of Solvation on the α- to 310-Helical Transition

Smythe M.L., Huston S.E. and Marshall G.R. (1995) The Molten Helix: Effects of Solvation on the α- to 310-Helical Transition. Journal of the American Chemical Society, 117 20: 5445-5452. doi:10.1021/ja00125a003


Author Smythe M.L.
Huston S.E.
Marshall G.R.
Title The Molten Helix: Effects of Solvation on the α- to 310-Helical Transition
Journal name Journal of the American Chemical Society   Check publisher's open access policy
ISSN 1520-5126
Publication date 1995-01-01
Year available 1995
Sub-type Article (original research)
DOI 10.1021/ja00125a003
Open Access Status Not yet assessed
Volume 117
Issue 20
Start page 5445
End page 5452
Total pages 8
Place of publication WASHINGTON
Publisher AMER CHEMICAL SOC
Language eng
Abstract Free energy surfaces, or potentials of mean force, for the alpha- to 3(10)-helical conformational transition in polypeptides have been calculated in several solvents of different dielectric. The alpha- to 3(10)-helical transition has been suggested as potentially important in various biological processes, including protein folding, formation of voltage-gated ion channels, kinetics of substrate binding in proteins, and signal transduction mechanisms. This study investigates the thermodynamics of the alpha- to 3(10)-helical transition of a model peptide, the capped decamer of alpha-methylalanine, in order to assess the plausibility of this transition in the mechanisms of such biological processes. The free energy surfaces indicate that in each environment studied the alpha-helical conformation is the more stable of the two for the decapeptide, The thermodynamic data suggest that the alpha-helix is energetically stabilized and the 3(10)-helix is entropically favored. The inclusion of dichloromethane, acetonitrile, or water results in approximately 7 kcal/mol of relative conformational energy (favoring the alpha-helix) and 3 kcal/mol of relative conformational entropy (favoring the 3(10)-helix) in comparison to the gas phase. In polar environments, the alpha-helix is stabilized by its more favorable salute-solvent electrostatic interactions, and solute-solute steric interactions. In addition, it was concluded that in polar solvents, especially water, it is possible for the peptide to reduce some of the inherent strain of the 3(10)-helix by widening psi, the resulting weaker intrasolute hydrogen bonds being compensated for by increased-hydrogen bonding to the solvent. Lower polarity environments are associated with a marginally increased relative stability of the 3(10)-helix, which we suggest is largely due to the additional intrahelical hydrogen bond of this conformation. The data suggest that, in environments such as membranes, the interior of proteins or crystals, the complete transition from an ct-helix to a 3(10)-helix for this decapeptide would require less than 6 kcal/mol in free energy. Switching conformations for individual residues is much more facile, and shorter 3(10)-helices may actually be energetically favored, at least, in nonpolar environments. This study primarily estimates the backbone contribution to the helical transition; side chain interactions would be expected to play a significant role in stabilizing one conformer relative to the other. It is, therefore, quite feasible that the alpha- to 3(10)-helical transition could provide a possible mechanism for many biological processes. While there are many factors, such as helix length and side chain packing, that contribute to the selection of either the alpha- or the 3(10)-helical conformation or a mixture of the two, this study focuses primarily on one of these effects, that of the polarity of the environment.
Keyword Molecular-Dynamics Simulations
Alpha,alpha-Dialkyl Amino-Acids
Monte-Carlo Simulations
Alanine-Based Peptides
Aminoisobutyric-Acid
Parallel Packing
S-Peptide
Proteins
Water
Preferences
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
 
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