On the stability of a single-turn alpha-helix: the single versus multiconformation problem.
The pentapeptide Ac-HAAAH-NH2, cyclized through its imidazoles by PdII to give [Pd(en)(peptide)]2+, has recently been evaluated by 2-D NMR and simulated annealing as a single alpha-helix conformation in solution. In the present work, we have questioned this assumption by developing Pd2+ parameters for AMBER*, performing an extensive conformational search for the [Pd(en)(peptide)]2+, and deconvoluting the averaged NMR data into eight rapidly equilibrating conformations with populations ranging from 2 to 55%. None of the latter correspond to the alpha-helix, although a 3% form possesses a related structure. As a critical component of interpreting an averaged NMR spectrum in terms of a single conformation, we advise testing this assumption with a method that permits conformational deconvolution.
Snyder
James P
JP
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA. snyder@euch4e.chem.emory.edu
Lakdawala
Ami S
AS
Kelso
Michael J
MJ
D006639:Histidine / Q000737:chemistry; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
D009842:Oligopeptides; D010456:Peptides, Cyclic; D006639:Histidine; D010165:Palladium