Journal
PROTEIN SCIENCE
Volume 12, Issue 6, Pages 1145-1157Publisher
WILEY
DOI: 10.1110/ps.0240103
Keywords
molecular dynamics; pi-helix; 3(10)-helix; force-shifted cutoff; conformational ensemble; helix-coil transition
Categories
Funding
- NIGMS NIH HHS [R01 GM050789, T32 GM 08268, GM 50789, R29 GM050789, T32 GM008268] Funding Source: Medline
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The conformational equilibrium between 3(10)- and alpha-helical structure has been studied via high-resolution NMR spectroscopy by Millhauser and coworkers using the MW peptide Ac-AMAAKAWAAKA AAARA-NH2. Their 750-MHz nuclear Overhauser effect spectroscopy (NOESY) spectra were interpreted to reflect appreciable populations of 3(10)-helix throughout the peptide, with the greatest contribution at the N and C termini. The presence of simultaneous alphaN(i,i + 2) and alphaN(i,i + 4) NOE cross-peaks was proposed to represent conformational averaging between 3(10)- and alpha-helical structures. In this study, we describe 25-nsec molecular dynamics simulations of the MW peptide at 298 K, using both an 8 A and a 10 A force-shifted nonbonded cutoff. The ensemble averages of both simulations are in reasonable agreement with the experimental helical content from circular dichroism (CD), the (3)J(HNalpha) coupling constants, and the 57 observed NOES. Analysis of the structures from both simulations revealed very little formation of contiguous i --> i + 3 hydrogen bonds (3(10)-helix); however, there was a large population of bifurcated i i + 3 and i --> i + 4 alpha-helical hydrogen bonds. In addition, both simulations contained considerable populations of pi-helix (i --> i + 5 hydrogen bonds). Individual turns formed over residues 1-9, which we predict contribute to the intensities of the experimentally observed alphaN(i,i + 2) NOES. Here we show how sampling of both folded and unfolded structures can provide a structural framework for deconvolution of the conformational contributions to experimental ensemble averages.
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