Taming conformational heterogeneity in and with vibrational circular dichroism spectroscopy
| Autor: | Mark A. J. Koenis, Valentin P. Nicu, Wybren Jan Buma, Lucas Visscher, Sérgio R. Domingos, Yiyin Xia |
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| Přispěvatelé: | Molecular Spectroscopy (HIMS, FNWI), Theoretical Chemistry, AIMMS |
| Rok vydání: | 2019 |
| Předmět: |
Physics
Flexibility (engineering) FELIX Condensed Matter Physics Quantitative Biology::Biomolecules 010405 organic chemistry Molecular and Biophysics General Chemistry Function (mathematics) 010402 general chemistry 01 natural sciences Spectral line 3. Good health 0104 chemical sciences Highly sensitive Chemistry ddc:540 Vibrational circular dichroism Statistical physics SDG 7 - Affordable and Clean Energy Spectroscopy Conformational isomerism Reliability (statistics) |
| Zdroj: | Chemical Science, 10, 7680-7689 Chemical Science, 10(33), 7680-7689. Royal Society of Chemistry Chemical Science, 10, 33, pp. 7680-7689 Koenis, M A J, Xia, Y, Domingos, S R, Visscher, L, Buma, W J & Nicu, V P 2019, ' Taming conformational heterogeneity in and with vibrational circular dichroism spectroscopy ', Chemical Science, vol. 10, no. 33, pp. 7680-7689 . https://doi.org/10.1039/c9sc02866h Chemical Science Chemical science 10, 7680-7689 (2019). doi:10.1039/C9SC02866H |
| ISSN: | 2041-6520 |
| DOI: | 10.1039/c9sc02866h |
| Popis: | Chemical science 10, 7680 -7689 (2019). doi:10.1039/C9SC02866H 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. Published by RSC, Cambridge |
| Databáze: | OpenAIRE |
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