Amide I Vibrational Properties Affected by Hydrogen Bonding Out-of-Plane of the Peptide Group

Abstract

The amide I vibrational properties of a peptide-water complex in various intermolecular configurations are analyzed theoretically to see whether a water molecule with a weak out-of-plane hydrogen bond really induces a large low-frequency shift. It is shown that the frequency shift strongly depends on the C═O···H angle, with a larger low-frequency shift as the C═O···H becomes more bent, suggesting that the so-called hydrated helix with a rather low amide I frequency has an additional water molecule located out-of-plane of the peptide group as compared with a typical α-helix. The infrared intensity also depends on the angular position of water. A new model parameter set (that can be combined with molecular dynamics) is developed for a more correct representation of the hydration-induced frequency shift. The question regarding the scalar and vectorial nature of the molecular properties related to the frequency shift is also discussed.

Communication: Quantitative multi-site frequency maps for amide I vibrational spectroscopy

“…As noted by Torii, such contributions can be induced by nuclear motion off the bond axis; in such cases, field-based (or mixed field/potential) maps may be superior to potential maps alone. 13 For amide I vibrations, however, our results suggest that field-and potential-based maps may be equally effective, making the choice between them a matter of convenience.…”

“…1 In addition to shedding light on bulk secondary structure content, amide I spectroscopy probes local protein structure and dynamics through the sensitivity of individual carbonyl frequencies to local electrostatics. 2 Experimentally, this local structural information is accessed by embedding 13 C or 13 C 18 O isotope labels into specific amide groups along the peptide backbone, spectrally isolating the absorption bands of the labeled sites. 2 This link between local structure and spectroscopic observables has long made the development of an accurate amide I spectral "map" a highly desirable goal.…”

“…12 For example, a recent study on hydrogen bonding of water to N-methylacetamide (NMA) compared 14 different amide I literature maps against ab initio calculations, finding wide variation in map predictions (often with opposing trends) and no clear agreement with the ab initio data. 13 To overcome this uncertainty, we have been developing experimental standards for amide I frequency maps. Our first dataset consisted of experimental absorption spectra from 28 dipeptide fragments in various protonation states in solution for a total of 73 reference frequencies.…”

“…Arguments have been made in favor of both field and potential maps, but neither has demonstrated a clear advantage. 3,5,13 To provide a more rigorous test of such models, we turned to isotope-enriched protein expression to produce five isotope-labeled variants of the protein G mutant NuG2b. 12 Each construct displays uniform 13 C 18 O labeling of all amide bonds immediately following a particular residue: Gly (3 sites), Ala (8 sites), Val (6 sites), Leu (2 sites), or Phe (3 sites).…”

“…3,5,13 To provide a more rigorous test of such models, we turned to isotope-enriched protein expression to produce five isotope-labeled variants of the protein G mutant NuG2b. 12 Each construct displays uniform 13 C 18 O labeling of all amide bonds immediately following a particular residue: Gly (3 sites), Ala (8 sites), Val (6 sites), Leu (2 sites), or Phe (3 sites). In contrast to the floppy, highly solvated dipeptides in our original study, the NuG2b labels probe mid-chain amide bonds in a variety of conformations in a protein of extreme structural stability.…”