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VCD spectroscopic and molecular dynamics analysis of the Trp‐cage miniprotein TC5b
Author(s) -
Copps Jeffrey,
Murphy Richard F.,
Lovas Sándor
Publication year - 2007
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20709
Subject(s) - polyproline helix , chemistry , circular dichroism , protein secondary structure , crystallography , vibrational circular dichroism , spectroscopy , peptide , nuclear magnetic resonance spectroscopy , solvent , molecular dynamics , aqueous solution , stereochemistry , computational chemistry , organic chemistry , biochemistry , quantum mechanics , physics
TC5b is a 20 residue polypeptide notable for its compact tertiary structure, a rarity for a short peptide. This structure is due to the “Trp‐cage“ motif, an association of aromatic, Pro, and Gly residues. The structure of TC5b has been fully characterized by NMR and electronic circular dichroism (ECD) studies, but has never been studied with vibrational circular dichroism (VCD) spectroscopy, which may reveal finer structure. In this study, we examine the VCD spectra of TC5b to characterize the spectroscopic signature of the peptide and its comprising structural elements. TC5b exhibited a negative‐positive‐negative triplet which is associated with α‐helical structure in deuterated solvents but also signs of a polyproline II (PPII) helix in the amide I' region. Detection of this element was complicated by the aforementioned triplet form, as well as by an upfrequency shift in PPII helical elements due to the use of the deuterated organic solvents DMSO‐d 6 and TFE‐d 1 . Nevertheless, while ECD spectra showed only α‐helical structure for TC5b, VCD spectroscopy revealed a more complex structure which was in agreement with NMR results. VCD spectroscopy also showed a rapid conformational change of the peptide at temperatures above 35°C in D 2 O and in aqueous solvent with greater than 75% DMSO‐d 6 content. Molecular dynamics (MD) simulations to investigate this latter effect of DMSO‐d 6 on TC5b were conducted in DMSO and 50% (v/v) DMSO in H 2 O. In DMSO unfolding of the peptide was rapid while in 50% (v/v) DMSO in H 2 O the unfolding was more gradual. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 427–437, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com