Conformational equilibrium in alanine-rich peptides probed by reversible stretching simulations.
Reversible stretching of the alanine-rich peptide 3K (Proc. Natl. Acad. Sci. USA 1989, 86, 5286-5290) and its analogue MW (Nature 1992, 359, 653-655) is examined using molecular dynamics simulations in explicit water. In both cases, sampling of the extension pathway is obtained on the 10 ns time scale by applying an adaptive biasing force. The free energy profile reveals a single minimum associated with a contiguous alpha-helix. Short 3(10)-helical motifs are observed in folded as well as extended conformations, in accordance with their proposed role as folding intermediates. The native 3(10)-helical content of both peptides is found, however, to be no higher than a few percent. Difficulties in both the definition and the detection of secondary structure motifs, most notably in relation to bifurcated hydrogen bonds, are proposed to account for the discrepancy between 3(10)-helical propensities reported by several authors, based on experimental and computational results.
Hénin
Jérôme
J
Equipe de Dynamique des Assemblages Membranaires, UMR CNRS/UHP No. 7565, Université Henri Poincaré, BP 239, 54506 Vandoeuvre-lès-Nancy Cedex, France.
Schulten
Klaus
K
Chipot
Christophe
C
D000409:Alanine / Q000737:chemistry*; D003198:Computer Simulation; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D010455:Peptides; D014867:Water; D000409:Alanine