Dataset Information

Analysis of Vibrational Circular Dichroism Spectra of Peptides: A Generalized Coupled Oscillator Approach of a Small Peptide Model Using VCDtools.

ABSTRACT: Vibrational circular dichroism (VCD) is one of the major spectroscopic tools to study peptides. Nevertheless, a full understanding of what determines the signs and intensities of VCD bands of these compounds in the amide I and amide II spectral regions is still far from complete. In the present work, we study the origin of these VCD signals using the general coupled oscillator (GCO) analysis, a novel approach that has recently been developed. We apply this approach to the ForValNHMe model peptide in both ?-helix and ?-sheet configurations. We show that the intense VCD signals observed in the amide I and amide II spectral regions essentially have the same underlying mechanism, namely, the through-space coupling of electric dipoles. The crucial role played by intramolecular hydrogen bonds in determining VCD intensities is also illustrated. Moreover, we find that the contributions to the rotational strengths, considered to be insignificant in standard VCD models, may have sizable magnitudes and can thus not always be neglected. In addition, the VCD robustness of the amide I and II modes has been investigated by monitoring the variation of the rotational strength and its contributing terms during linear transit scans and by performing calculations with different computational parameters. From these studies-and in particular, the decomposition of the rotational strength made possible by the GCO analysis-it becomes clear that one should be cautious when employing measures of robustness as proposed previously.

SUBMITTER: Koenis MAJ

PROVIDER: S-EPMC7061330 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Analysis of Vibrational Circular Dichroism Spectra of Peptides: A Generalized Coupled Oscillator Approach of a Small Peptide Model Using VCDtools.

Koenis Mark A J MAJ Visscher Lucas L Buma Wybren J WJ Nicu Valentin P VP

The journal of physical chemistry. B 20200221 9

Vibrational circular dichroism (VCD) is one of the major spectroscopic tools to study peptides. Nevertheless, a full understanding of what determines the signs and intensities of VCD bands of these compounds in the amide I and amide II spectral regions is still far from complete. In the present work, we study the origin of these VCD signals using the general coupled oscillator (GCO) analysis, a novel approach that has recently been developed. We apply this approach to the ForValNHMe model peptid ...[more]

PMID: 32037822

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Project description:Cyclic peptides are a promising class of compounds for next-generation antibiotics as they may provide new ways of limiting antibiotic resistance development. Although their cyclic structure will introduce some rigidity, their conformational space is large and they usually have multiple chiral centers that give rise to a wide range of possible stereoisomers. Chiroptical spectroscopies such as vibrational circular dichroism (VCD) are used to assign stereochemistry and discriminate enantiomers of chiral molecules, often in combination with electronic structure methods. The reliable determination of the absolute configuration of cyclic peptides will require robust computational methods than can identify all significant conformers and their relative population and reliably assign their stereochemistry from their chiroptical spectra by comparison with ab initio calculated spectra. We here present a computational protocol for the accurate calculation of the VCD spectra of a series of flexible cyclic oligopeptides. The protocol builds on the Conformer-Rotamer Ensemble Sampling Tool (CREST) developed by Grimme and co-workers ( Phys. Chem. Chem. Phys. 2020, 22, 7169-7192 and J. Chem. Theory. Comput. 2019, 15, 2847-2862) in combination with postoptimizations using B3LYP and moderately sized basis sets. Our recommended computational protocol for the computation of VCD spectra of cyclic oligopeptides consists of three steps: (1) conformational sampling with CREST and tight-binding density functional theory (xTB); (2) energy ranking based on single-point energy calculations as well as geometry optimization and VCD calculations of conformers that are within 2.5 kcal/mol of the most stable conformer using B3LYP/6-31+G*/CPCM; and (3) VCD spectra generation based on Boltzmann weighting with Gibbs free energies. Our protocol provides a feasible basis for generating VCD spectra also for larger cyclic peptides of biological/pharmaceutical interest and can thus be used to investigate promising compounds for next-generation antibiotics.

Dataset Information

Analysis of Vibrational Circular Dichroism Spectra of Peptides: A Generalized Coupled Oscillator Approach of a Small Peptide Model Using VCDtools.

Publications

Analysis of Vibrational Circular Dichroism Spectra of Peptides: A Generalized Coupled Oscillator Approach of a Small Peptide Model Using VCDtools.

Similar Datasets

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