Issue 33, 2019

Taming conformational heterogeneity in and with vibrational circular dichroism spectroscopy

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

Supplementary files

Article information

Article type
Edge Article
Submitted
12 Jun 2019
Accepted
08 Jul 2019
First published
09 Jul 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 7680-7689

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

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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