Volume 6 Supplement 1

9th German Conference on Chemoinformatics

Open Access

QM quality atomic charges for proteins

  • Stanislav Geidl1Email author,
  • Crina-Maria Ionescu1,
  • Radka Svobodová Vařeková1 and
  • Jaroslav Koča1
Journal of Cheminformatics20146(Suppl 1):P61

DOI: 10.1186/1758-2946-6-S1-P61

Published: 11 March 2014

The concept of atomic point charges is well established in theoretical chemistry. Atomic point charges have played an important role in understanding and modeling chemical behavior by allowing to extract and quantify information stored in the molecular electron distribution of chemical compounds. Thus, atomic point charges have been used to estimate reactivity indices, dissociation constants, partition coefficients, the electrostatic contribution in molecular dynamics or docking studies. It is therefore desirable to have knowledge of the values of atomic charges in proteins (see, e.g., [1]). Unfortunately, accurate and universally applicable approaches for atomic charge calculation based on quantum mechanics (QM) are very time consuming and thus cannot be employed for large biomolecules like proteins. An alternative is to use empirical charge calculation methods, such as the electronegativity equalization method (EEM) [2], which is very fast and has accuracy comparable to QM. The challenge is to calibrate (i.e., parametrize) this method for proteins. This parameterization can be done using atomic charges calculated by different types of QM approaches. EEM can be as accurate as the QM approach for which EEM was calibrated.

In our work, we present the workflow of the EEM calibration process. Afterwards, we calibrate and validate EEM models for 12 types of QM charges, including the newest approaches like iterative Hirshfeld [3]. The accuracy of the obtained EEM models is evaluated on insulin and ubiquitin. We also show two case studies demonstrating the applicability of atomic charges computed via EEM: a small docking study, and the calculation of electrostatic potential based on the EEM charges [4].

Authors’ Affiliations

(1)
National Centre for Biomolecular Research, Faculty of Science and CEITEC - Central European Institute of Technology, Masaryk University

References

  1. Ionescu CM, Svobodová Vařeková R, Prehn JH, Huber HJ, Koča J: Charge profile analysis reveals that activation of pro-apoptotic regulators Bax and Bak relies on charge transfer mediated allosteric regulation. PLoS computational biology. 2012, 8 (6): e1002565-10.1371/journal.pcbi.1002565.View ArticleGoogle Scholar
  2. Mortier WJ, Vangenechten K, Gasteiger J: Electronegativity Equalization - Application and Parametrization. J Am Chem Soc. 1985, 107: 829-835. 10.1021/ja00290a017.View ArticleGoogle Scholar
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  4. Ionescu CM, Geidl S, Svobodová Vařeková R, Koča J: Rapid calculation of accurate atomic charges for proteins via the electronegativity equalization method. J Chem Inf Model. 2013,Google Scholar

Copyright

© Geidl 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.