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Structural insights for designed alanine‐rich helices: Comparing NMR helicity measures and conformational ensembles from molecular dynamics simulation
Author(s) -
Song Kun,
Stewart James M.,
Fesinmeyer R. Matthew,
Andersen Niels H.,
Simmerling Carlos
Publication year - 2008
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21004
Subject(s) - chemistry , intramolecular force , crystallography , helix (gastropod) , molecular dynamics , solvation , helicity , hydrogen bond , stereochemistry , computational chemistry , molecule , physics , ecology , organic chemistry , particle physics , snail , biology
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 α‐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. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 747–760, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com