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Different degrees of disorder in long disordered peptides can be discriminated by vibrational spectroscopy
Journal article

Different degrees of disorder in long disordered peptides can be discriminated by vibrational spectroscopy

Reinhard Schweitzer-Stenner
The journal of physical chemistry. B, v 117(23), pp 6927-6936
13 Jun 2013
PMID: 23631686

Abstract

Peptide Fragments - chemistry Spectrophotometry, Infrared Magnetic Resonance Spectroscopy Peptides - chemistry Protein Structure, Secondary Protein Unfolding Calcitonin - chemistry Amyloid beta-Peptides - chemistry Molecular Dynamics Simulation
The isotropic Raman, anisotropic Raman, IR, and vibrational circular dichroism (VCD) amide I profiles of a 20 residue homopeptide were calculated for different conformational mixtures that one would generally characterize as random coil or disordered. We first show that (1) pure polyproline II (pPII) coils, (2) statistical coils with different fractions pPII, β-strand, and right-handed helical residue conformations, and (3) ideal random coils (nearly equal probabilities for pPII, β, and right-handed helical) can be discriminated based on their respective VCD signal and, to a more limited extent, by means of the peak positions and asymmetries of the corresponding IR and Raman bands. Since molecular dynamics (MD) simulations of unfolded peptides (e.g., Aβ-segments) suggest a mixture of statistical coil and temporarily folded conformations, we calculated the amide I profiles of such mixtures composed of helical, β-strand, and disordered conformers and show that they give rise to rather distinct amide I profiles. Mixtures of regular structures with statistical coil segments can be discriminated from pure statistical and random coils by the amplitude of the negative amide I couplet in the VCD spectrum. We finally demonstrate the usefulness of such simulations by applying them to monomeric state of salmon calcitonin and the amyloid β fragment Aβ1-28, for which NMR data provide evidence for a coexistence between statistical coil and helical conformations. Altogether, our results show that the combined use of the four amide I profiles provides spectroscopists with a powerful tool to discriminate between different conformational manifolds that long unfolded and disordered peptides and proteins might adopt in solution.

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Web of Science research areas
Biophysics
Chemistry, Physical
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