title: 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).
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).
authors.affiliation: Institute for Biocomplexity and Informatics and Department for Biological Sciences, 2500 University Drive, Calgary, Alberta, Canada T2N1N4. blev@ucalgary.ca
authors.forename: Bogdan
authors.initials: B
authors.lastname: Lev
authors.forename: Sergei Yu
authors.initials: SY
authors.lastname: Noskov
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000737:chemistry* / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism*; D001665:Binding Sites; D002414:Cations, Monovalent / Q000737:chemistry*; D018360:Crystallography, X-Ray; D056004:Molecular Dynamics Simulation; D012964:Sodium / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D027322:Amino Acid Transport System X-AG; D002414:Cations, Monovalent; D001224:Aspartic Acid; D012964:Sodium