Taming conformational heterogeneity in and with vibrational circular dichroism spectroscopy

Mark A.J. Koenis, Yiyin Xia, Sérgio R. Domingos, Lucas Visscher, Wybren J. Buma*, Valentin P. Nicu

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)7680-7689
Number of pages10
JournalChemical Science
Issue number33
Publication statusPublished - 9 Jul 2019


VPN acknowledges funding from UEFISCDI (PN-III-P1-1.1-TE-2016-1049, contract Nr. 46/2018). MAJK, LV and WJB acknowledge nancial support from NWO in the framework of the Fund New Chemical Innovations (NWO Project Nr. 731.014.209).

FundersFunder number
Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii


    Dive into the research topics of 'Taming conformational heterogeneity in and with vibrational circular dichroism spectroscopy'. Together they form a unique fingerprint.

    Cite this