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

Darón I Freedberg; Richard M Venable; Angelo Rossi; Thomas E Bull; Richard W Pastor

doi:10.1021/ja0484146

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

J Am Chem Soc. 2004 Aug 25;126(33):10478-84. doi: 10.1021/ja0484146.

Authors

Darón I Freedberg¹, Richard M Venable, Angelo Rossi, Thomas E Bull, Richard W Pastor

Affiliation

¹ Contribution from the Laboratory of Biophysics, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, USA.

PMID: 15315464
DOI: 10.1021/ja0484146

Abstract

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.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Alanine / chemistry
Carbon Isotopes
Circular Dichroism
Computer Simulation
Hydrogen Bonding
Nitrogen Isotopes
Nuclear Magnetic Resonance, Biomolecular / methods*
Peptides / chemistry*
Protein Structure, Secondary
Ubiquitin / chemistry

Substances

Carbon Isotopes
Nitrogen Isotopes
Peptides
Ubiquitin
Alanine