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Distribution of conformations sampled by the central amino acid residue in tripeptides inferred from amide I band profiles and NMR scalar coupling constants
Journal article

Distribution of conformations sampled by the central amino acid residue in tripeptides inferred from amide I band profiles and NMR scalar coupling constants

Reinhard Schweitzer-Stenner
The journal of physical chemistry. B, v 113(9), pp 2922-2932
05 Mar 2009
PMID: 19243204

Abstract

Models, Theoretical Magnetic Resonance Spectroscopy - methods Peptides - chemistry Protein Structure, Secondary Molecular Conformation Amino Acids - chemistry Alanine - chemistry Spectrum Analysis, Raman - methods Models, Statistical Spectrophotometry, Infrared - methods Algorithms Anisotropy Water - chemistry Amides - chemistry Oligopeptides - chemistry
The conformational preference of individual amino acid residues in the unfolded state of peptides and proteins is the subject of a continuous debate. Research has mostly been focused on alanine, owing to its abundance in proteins and its relevance for the understanding of helix <---> coil transitions. In the current study, we have analyzed the amide I band profiles of the IR, isotropic and anisotropic Raman, and VCD profiles of trialanine in terms of a conformational model which, for the first time, explicitly considers the entire ensemble of possible conformations rather than representative structures. The distribution function utilized for a satisfactory simulation of the amide I band profiles was found to also reproduce a set of five J coupling constants reported by Graf et al. (Graf, J.; et al. J. Am. Chem. Soc. 2007, 129, 1179). The results of our analysis reveal a PPII fraction of approximately 0.84 for the central alanine residue, which strongly corroborates the notion that alanine has a very high PPII propensity, exceeding the values obtained from restricted coil libraries. We performed a similar analysis for trivaline and found that the dominant fraction of its central residue is a beta-strand. The fraction of the respective distribution is 0.68. The remaining fraction contains contributions from helical and PPII conformations. The results of our analysis enable us to decide on the suitability of force fields used for MD simulations of short alanine-containing peptides. The paper establishes vibrational spectroscopy as a suitable method to explore the energy landscape of amino acid residues.

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