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Improving the description of interactions between Ca2+ and protein carboxylate groups, including γ-carboxyglutamic acid: revised CHARMM22∗ parameters

Church, Andrew T., Hughes, Zak E. and Walsh, Tiffany R. 2015, Improving the description of interactions between Ca2+ and protein carboxylate groups, including γ-carboxyglutamic acid: revised CHARMM22∗ parameters, RSC Advances, vol. 5, no. 83, pp. 67820-67828, doi: 10.1039/c5ra11268k.

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Title Improving the description of interactions between Ca2+ and protein carboxylate groups, including γ-carboxyglutamic acid: revised CHARMM22∗ parameters
Formatted title Improving the description of interactions between Ca<sup>2+</sup> and protein carboxylate groups, including γ-carboxyglutamic acid: revised CHARMM22∗ parameters
Author(s) Church, Andrew T.
Hughes, Zak E.ORCID iD for Hughes, Zak E. orcid.org/0000-0003-2166-9822
Walsh, Tiffany R.ORCID iD for Walsh, Tiffany R. orcid.org/0000-0002-0233-9484
Journal name RSC Advances
Volume number 5
Issue number 83
Start page 67820
End page 67828
Total pages 9
Publisher Royal Society of Chemistry
Place of publication Cambridge, Eng.
Publication date 2015-07-30
ISSN 2046-2069
Summary A reliable description of ion pair interactions for biological systems, particularly those involving polyatomic ions such as carboxylate and divalent ions such as Ca2+, using biomolecular force-fields is essential for making useful predictions for a range of protein functions. In particular, the interaction of divalent ions with the double carboxylate group present in γ-carboxyglutamic acid (Gla), relevant to the function of many proteins, is relatively understudied using biomolecular force-fields. Using force-field based metadynamics simulations to predict the free energy of binding between Ca2+ and the carboxylate group in liquid water, we show that a widely-used biomolecular force-field, CHARMM22∗, substantially over-estimates the binding strength between Ca2+ and the side-chains of both glutamic acid (Glu) and Gla, compared with experimental data obtained for the analogous systems of aqueous calcium-acetate and calcium-malonate. To correct for this, we propose and test a range of modifications to the σ value of the heteroatomic Lennard-Jones interaction between Ca2+ and the oxygen of the carboxylate group. Our revised parameter set can recover the same three association modes of this aqueous ion pair as the standard parameter set, and yields free energies of binding for the carboxylate-Ca2+ interaction in good agreement with experimental data. The revised parameter set recovers other structural properties of the ion pair in agreement with the standard CHARMM22∗ parameter set.
Language eng
DOI 10.1039/c5ra11268k
Field of Research 030704 Statistical Mechanics in Chemistry
030402 Biomolecular Modelling and Design
Socio Economic Objective 970103 Expanding Knowledge in the Chemical Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Royal Society of Chemistry
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30077025

Document type: Journal Article
Collections: Institute for Frontier Materials
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.