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Issue 33, 2019
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Taming conformational heterogeneity in and with vibrational circular dichroism spectroscopy

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Abstract

The flexibility of a molecule has important consequences on its function and application. Vibrational Circular Dichroism (VCD) is intrinsically an excellent experimental technique to get a hold on this flexibility as it is highly sensitive to key conformational details and able to distinguish rapidly interconverting conformers. One of the major challenges in analyzing the spectra by comparison to theoretical predictions is the uncertainty in the computed energies of the multitude of conformations. This uncertainty also affects the reliability of the stereochemical assignment it is normally used for. We present here a novel approach that explicitly takes the energy uncertainties into account in a genetic algorithm based method that fits calculated to the experimental spectra. We show that this approach leads to significant improvements over previously used methodologies. Importantly, statistical validation studies provide quantitative measures for the reliability of relevant parameters used such as the energy uncertainty and the extent to which conformational heterogeneity can be determined. Similarly, quantitative measures can be obtained for the possibility that the flexibility that is introduced in the fit might lead to an incorrect assignment of the stereochemistry. These results break new ground for different techniques based on VCD to elucidate conformational flexibility.

Graphical abstract: Taming conformational heterogeneity in and with vibrational circular dichroism spectroscopy

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Publication details

The article was received on 12 Jun 2019, accepted on 08 Jul 2019 and first published on 09 Jul 2019


Article type: Edge Article
DOI: 10.1039/C9SC02866H
Chem. Sci., 2019,10, 7680-7689
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Taming conformational heterogeneity in and with vibrational circular dichroism spectroscopy

    M. A. J. Koenis, Y. Xia, S. R. Domingos, L. Visscher, W. J. Buma and V. P. Nicu, Chem. Sci., 2019, 10, 7680
    DOI: 10.1039/C9SC02866H

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