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. Attached Files Name Description MIMEType Size Downloads church-improvingthe-2015.pdf Published version application/pdf 2.83MB 109 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.org/0000-0003-2166-9822 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 Open Access Collection GTP Research Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. 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. Versions Version Filter Type Thu, 27 Aug 2015, 08:06:33 EST Mon, 31 Aug 2015, 14:04:20 EST Tue, 01 Sep 2015, 05:01:41 EST Tue, 01 Sep 2015, 06:12:39 EST Tue, 01 Sep 2015, 10:37:27 EST Tue, 01 Sep 2015, 10:39:17 EST Tue, 01 Sep 2015, 10:43:50 EST Wed, 07 Sep 2016, 10:16:03 EST Wed, 06 Dec 2017, 06:16:27 EST Fri, 07 Sep 2018, 17:37:54 EST Filtered Full Citation counts:   Cited 7 times in TR Web of Science Cited 7 times in Scopus Search Google Scholar Access Statistics: 486 Abstract Views, 110 File Downloads  -  Detailed Statistics Created: Mon, 31 Aug 2015, 14:04:20 EST

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.