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Updated: Jul 5, 2026

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
Structural insights for designed alanine-rich helices: comparing NMR helicity measures and conformational ensembles
Kun Song1, James M Stewart, R Matthew Fesinmeyer
1Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.
Abstract:
The temperature dependence of helical propensities for the peptides Ac-ZGG-(KAAAA)(3)X-NH(2) (Z = Y or G, X = A, K, and D-Arg) were studied both experimentally and by MD simulations. Good agreement is observed in both the absolute helical propensities as well as relative helical content along the sequence; the global minimum on the calculated free energy landscape corresponds to a single alpha-helical conformation running from K4 to A18 with some terminal fraying, particularly at the C-terminus. Energy component analysis shows that the single helix state has favorable intramolecular electrostatic energy due to hydrogen bonds, and that less-favorable two-helix globular states have favorable solvation energy. The central lysine residues do not appear to increase helicity; however, both experimental and simulation studies show increasing helicity in the series X = Ala --> Lys --> D-Arg. This C-capping preference was also experimentally confirmed in Ac-(KAAAA)(3)X-GY-NH(2) and (KAAAA)(3)X-GY-NH(2) sequences. The roles of the C-capping groups, and of lysines throughout the sequence, in the MD-derived ensembles are analyzed in detail.
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