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Conformational Preferences of a β ‐Octapeptide as Function of Solvent and Force‐Field Parameters
Author(s) -
Choutko Alexandra,
van Gunsteren Wilfred F.
Publication year - 2013
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201200173
Subject(s) - chemistry , biomolecule , peptide , nuclear magnetic resonance spectroscopy , molecule , force field (fiction) , chemical shift , conformational ensembles , peptide conformation , nuclear overhauser effect , helix (gastropod) , computational chemistry , crystallography , molecular dynamics , stereochemistry , organic chemistry , physics , biochemistry , quantum mechanics , ecology , snail , biology
Abstract The ability to design properly folded β ‐peptides with specific biological activities requires detailed insight into the relationship between the amino acid sequence and the secondary and/or tertiary structure of the peptide. One of the most frequently used spectroscopic techniques for resolving the structure of a biomolecule is NMR spectroscopy. Because only signal intensities and frequencies are recorded in the experiment, a conformational interpretation of the recorded data is not straightforward, especially for flexible molecules. The occurrence of conformational and/or time averaging, and the limited amount and accuracy of experimental data hamper the precise conformational determination of a biomolecule. In addition, the relation between experimental observables with the underlying conformational ensemble is often only approximately known, thereby aggravating the difficulty of structure determination of biomolecules. The problematic aspects of structure refinement based on NMR nuclear Overhauser effect (NOE) intensities and 3 J ‐coupling data are illustrated by simulating a β ‐octapeptide in explicit MeOH and H 2 O as solvents using three different force fields. NMR Data indicated that this peptide would fold into a 3 14 ‐helix in MeOH and into a hairpin in H 2 O. Our analysis focused on the conformational space visited by the peptide, on structural properties of the peptide, and on agreement of the MD trajectories with available NMR data. We conclude that 1 ) although the 3 14 ‐helical structure is present when the peptide is solvated in MeOH, it is not the only relevant conformation, and that 2 ) the NMR data set available for the peptide, when solvated in H 2 O, does not provide sufficient information to derive a single secondary structure, but rather a multitude of folds that fulfill the NOE data set.