Role of protein matrix rigidity and local polarization effects in the monovalent cation selectivity of crystallographic sites in the Na-coupled aspartate transporter GltPh

Bogdan Lev; Sergei Yu. Noskov

doi:10.1039/C2CP42860A

Role of proteinmatrix rigidity and local polarization effects in the monovalent cation selectivity of crystallographic sites in the Na-coupled aspartate transporter Glt_Ph

Bogdan Lev †^a and Sergei Yu. Noskov*^a

* Corresponding authors

^a Institute for Biocomplexity and Informatics and Department for Biological Sciences, 2500 University Drive, Calgary, Alberta, Canada
E-mail: snoskov@ucalgary.ca, blev@ucalgary.ca
Fax: +1-403-210-8655
Tel: +1-403-210-7971

Abstract

We have studied Li⁺/Na⁺/K⁺ selectivity of the bacterial aspartate transporter Glt_Ph using all-atom molecular dynamics (MD) and free energy simulations (FES) to evaluate the role of different factors that control ion preferences of the binding sites identified in the crystallographic structure. The role of the bound ions in stabilizing the hairpin loop (HP2) by acting as an extracellular gate is discussed. Free energy simulations with classical and polarizable force-fields were used to characterize the role of the protein matrix, the site composition and the induced polarization in the stabilization of native and non-native cations, such as Li⁺ and K⁺, in the ion-binding sites of the transporter. The role of different factors that control the selectivity of the binding sites was highlighted with a number of reduced models using a scheme recently developed by Yu et al. (Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 20329–20334 and J. Phys. Chem. B, 2009, 113, 8725).

Article information

https://doi.org/10.1039/C2CP42860A

Article type

Paper

Submitted

15 Aug 2012

Accepted

07 Dec 2012

First published

07 Dec 2012

Download Citation

Phys. Chem. Chem. Phys., 2013,15, 2397-2404

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Role of protein matrix rigidity and local polarization effects in the monovalent cation selectivity of crystallographic sites in the Na-coupled aspartate transporter Glt_Ph

B. Lev and S. Yu. Noskov, Phys. Chem. Chem. Phys., 2013, 15, 2397 DOI: 10.1039/C2CP42860A

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