title: Structural insights for designed alanine-rich helices: comparing NMR helicity measures and conformational ensembles from molecular dynamics simulation.
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.
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Song
authors.forename: James M
authors.initials: JM
authors.lastname: Stewart
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Fesinmeyer
authors.forename: Niels H
authors.initials: NH
authors.lastname: Andersen
authors.forename: Carlos
authors.initials: C
authors.lastname: Simmerling
mesh_terms: D003198:Computer Simulation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides