Institute for Biocomplexity and Informatics and Department for Biological Sciences, 2500 University Drive, Calgary, Alberta, Canada T2N1N4.
Phys Chem Chem Phys. 2013 Feb 21;15(7):2397-404. doi: 10.1039/c2cp42860a. Epub 2013 Jan 9.
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).
我们使用全原子分子动力学（MD）和自由能模拟（FES）研究了细菌天冬氨酸转运蛋白 Glt(Ph) 的 Li(+)/Na(+)/K(+) 选择性，以评估控制晶体结构中鉴定的结合位点离子偏好的不同因素的作用。讨论了结合离子通过充当细胞外门来稳定发夹环 (HP2) 的作用。使用经典和极化力场的自由能模拟用于表征蛋白质基质、位点组成和诱导极化在稳定天然和非天然阳离子（如 Li(+) 和 K(+)）在转运蛋白的离子结合位点中的作用。Yu 等人最近开发的一种方案（Proc. Natl. Acad. Sci. U. S. A.，2010，107，20329-20334 和 J. Phys. Chem. B，2009，113，8725）强调了控制结合位点选择性的不同因素的作用。
