Scientific Publications by FDA Staff

J Am Chem Soc 2004 Aug 25;126(33):10478-84

Discriminating the helical forms of peptides by NMR and molecular dynamics simulation.

Freedberg DI, Venable RM, Rossi A, Bull TE, Pastor RW

Pastor R, US FDA, Ctr Biol Evaluat & Res, Biophys Lab, 1401 Rockville Pike, Rockville, MD 20852 USA US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA

The HNCO NMR pulse sequence was applied to three selectively labeled (15)N and (13)C isotopic homologues of the peptide Ac-WAAAH(AAARA)(3)A-NH(2) to probe directly for hydrogen bonds between residues 8 and 11 (characteristic of a 3(10)-helix), 8 and 12 (alpha-helix), and 8 and 13 (pi-helix). The experiments demonstrate conclusively, and in agreement with circular dichroism studies, that the center of the peptide is alpha-helical; there is no discernible 3(10)- or pi-helix at these specific positions. Molecular dynamics simulations of the preceding peptide and Ac-(AAAAK)(3)A-NH(2) in water using the potential energy parameter set CHARMM22/CMAP correctly yield an alpha-helix, in contrast to simulations with the set CHARMM22, which result in a pi-helix.