Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/124650
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Type: Journal article
Title: Comparing nonbonded metal Ion models in the divalent cation binding protein PsaA
Author: MacDermott-Opeskin, H.
McDevitt, C.A.
O'Mara, M.L.
Citation: Journal of Chemical Theory and Computation, 2020; 16(3):1913-1923
Publisher: American Chemical Society
Issue Date: 2020
ISSN: 1549-9618
1549-9626
Statement of
Responsibility: 
Hugo MacDermott-Opeskin, Christopher A. McDevitt, Megan L. O’Mara
Abstract: Divalent metal cations are essential for many biological processes; however, accurately modeling divalent metal ions has proved a significant challenge for molecular dynamics force fields. Here we show that the choice of ion model influences the observed dynamics in PsaA, a metal binding protein from Streptococcus pneumoniae. We conduct extensive unbiased simulations and free energy calculations of PsaA bound to its cognate ligand Mn2+ and inhibitory ligand Zn2+ using three nonbonded ion models: a 12-6 model, a 12-6-4 model, and a multisite model. The observed coordination geometries and metal binding dynamics are sensitive to the choice of ion model, with the most dramatic differences observed in free energy calculations of ion release. We show that the conformational ensemble of Mn-bound PsaA is more similar to the crystallographic metal bound open state. This work extends the current model of PsaA metal binding and provides a framework for the rationalization of experimentally determined metal binding behavior. Our findings support the use of the 12-6-4 ion model for further simulations of divalent cation binding proteins.
Keywords: Humans; Streptococcus pneumoniae; Cations, Divalent; Metals; Carrier Proteins; Molecular Conformation
Rights: © 2020 American Chemical Society
RMID: 1000014772
DOI: 10.1021/acs.jctc.9b01180
Grant ID: http://purl.org/au-research/grants/arc/LE170100200
http://purl.org/au-research/grants/arc/FT170100006
http://purl.org/au-research/grants/nhmrc/1140554
Appears in Collections:Chemistry publications

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