Volume 6 Supplement 1

9th German Conference on Chemoinformatics

Open Access

Can quantum-chemical NMR chemical shifts be used as criterion for force-field development

  • Thomas E Exner1, 2Email author,
  • Andrea Frank2,
  • Heiko M Möller2 and
  • Martin Dračínský3
Journal of Cheminformatics20146(Suppl 1):O2

https://doi.org/10.1186/1758-2946-6-S1-O2

Published: 11 March 2014

Fragment-based quantum chemical calculations based on our adjustable density matrix assembler (ADMA) are able to calculate NMR chemical shifts even for proteins and protein-protein complexes [1, 2]. The agreement between the calculated and experimental chemical shifts in these calculations is, however, highly dependent on including conformational sampling and explicit solvent molecules. On the one hand, ensembles taken from classical MD simulations are suited for 13C and 1H chemical shift calculations if polar protons are neglected [3]. On the other hand, input structures from a Car–Parrinello MD resulted in landmark improvements over calculations based on classical MD especially for amide protons, which are predicted too high-field shifted based on the latter ensembles [4]. The better results are caused by the solute–solvents interactions forming shorter hydrogen bonds as well as by the internal degrees of freedom of the solute. With the obtained accuracy and the possibility of identifying the structural reasons for discrepancies between the experimental and calculated data, NMR chemical-shift calculations are now a perfect tool for e.g. the validation of new, improved force fields.

Authors’ Affiliations

(1)
Institute of Pharmacy, University of Tübingen
(2)
Department of Chemistry, University of Konstanz
(3)
Institute of Organic Chemistry and Biochemistry, Academy of Sciences

References

  1. Frank A, Onila I, Möller HM, Exner TE: Toward the Quantum Chemical Calculation of NMR Chemical Shifts of Proteins. Proteins. 2011, 79: 2189-2202. 10.1002/prot.23041.View ArticleGoogle Scholar
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  4. Dračínský M, Möller HM, Exner TE: Conformational Sampling by Ab Initio Molecular Dynamics Simulations Improves NMR Chemical Shift Predictions. J Chem Theory Comput. 2013, 9: 3806-3815. 10.1021/ct400282h. DOI:10.1021/ct400282hView ArticleGoogle Scholar

Copyright

© Exner et al; licensee Chemistry Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.