Structural insights for designed alanine-rich helices: comparing NMR helicity measures and conformational ensembles from molecular dynamics simulation.

Full 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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Author information

Author/s: Song, Kun (K); Stewart, James M (JM); Fesinmeyer, R Matthew (RM); Andersen, Niels H (NH); Simmerling, Carlos (C);

Affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.

Grants: GM 61678 (Agency:United States NIGMS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Biopolymers (Biopolymers), published in United States. (Language: eng)

Reference: 2008-Sep; vol 89 (issue 9) : pp 747-60

Dates: Created 2008/06/24; Completed 2008/08/19;

PMID: 18428207, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Computer Simulation
Hydrogen Bonding
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular

Nuclear Magnetic Resonance, Biomolecular
Oligopeptides - chemistry
Protein Structure, Secondary
Thermodynamics

Associated Chemicals: Oligopeptides (0)

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