Probing the competition between secondary structures and local preferences in gas phase isolated peptide backbones

Abstract

Combining laser desorption with a supersonic expansion together with the selectivity of IR/UV double resonance spectroscopy makes it possible to isolate and characterise the gas phase of remarkable backbone conformations of short peptide chains mimicking protein segments. A systematic bottom-up approach involving a conformer-specific IR study of peptide sequences of increasing sizes has enabled us to map the spectral signatures of the intramolecular interactions, which shape the peptide backbone, in particular H-bonds. The precise data collected are directly comparable to the most sophisticated quantum chemistry calculations of these species and therefore constitute a stringent test for the theoretical methods used. One-residue chains reveal the local conformational preference of the backbone and its dependence upon the nature of the residue. The investigation of longer chains provides evidence for a competition between simple successions of local conformational preferences along the chain and more folded structures, in which a new H-bonding network, involving distant H-bonding sites along the backbone, takes place. From three residues, the issue of helical folding can also be addressed. The present review of the gas phase literature data emphasizes the observation of remarkable secondary structures of biology, including short segments of beta-strands, gamma- and beta-turns, combinations of turns, including a 3(10) helix. It also provides evidence for the flexibility of the peptide chains, i.e., a critical influence of rather minor interactions (like side-chain/backbone interactions) on the conformational stability. Finally, the paper will discuss future promising directions of the present approach.

Unraveling the Stability of Polypeptide Helices: Critical Role of van der Waals Interactions

“…A truly bottom-up understanding of polypeptide structure and dynamics would greatly benefit from a first-principles quantum-mechanical treatment, as it becomes increasingly more feasible for large systems and long time scales. In particular, quantum-mechanical simulations in vacuo are invaluable for a quantitative understanding of the intramolecular forces that largely control the structure, stability and (un) folding dynamics of polypeptides.Recent progress in the experimental isolation and spectroscopies of gas-phase biological molecules has lead to increasingly refined vibrational spectra for the structure of peptides and proteins [4][5][6]. In fact, in vacuo proteins frequently preserve the secondary structure (helices and sheets) observed in solution, and recent results [7] have shown that even tertiary and quaternary structures can be transferred into the gas phase.…”

“…Recent progress in the experimental isolation and spectroscopies of gas-phase biological molecules has lead to increasingly refined vibrational spectra for the structure of peptides and proteins [4][5][6]. In fact, in vacuo proteins frequently preserve the secondary structure (helices and sheets) observed in solution, and recent results [7] have shown that even tertiary and quaternary structures can be transferred into the gas phase.…”

Preferred Configurations of Peptide–Peptide Interactions

“…And as one might expect, the importance of the peptide-peptide interaction has motivated a good deal of prior theoretical scrutiny [18][19][20][21][22][23][24] . Due to the delicacy involved in comparisons of different sorts of geometries, with differing origins of stability, it would be injudicious to base any decisions of relative stability on any but high-level correlated calculations, of which there have been several performed in recent years.…”

Mid-IRspectra of different conformers of phenylalanine in the gas phase

“…5 Conformer selective IR spectroscopy in the gas phase has been applied to various interesting systems, such as isolated or paired nucleobases, 6 to the amino-acids phenylalanine 4 and tryptophan, 7,8 to beta-sheet model systems 9 and other small peptides. 10,11 Most of these experiments have been performed using laser systems that cover the near-and mid-IR and are limited to wavelengths shorter than about 7 mm. In this range X-H (X ¼ C, O, N) and CQO stretching vibrations are probed and the experiments provide an insight into the conformational arrangement, as those vibrational transitions exhibit shifts in absorption frequency and changes in intensity in the presence of, for instance, intramolecular hydrogen bonds or solvating molecules.…”