Combined QM/MM Study of the Translocation of Chloride Ions through Escherichia Coli Chloride Ion Transporters

Abstract

Chloride ion transporters (ClC) move Cl- across cellular membranes and are associated with numerous physiological and cellular processes. However, despite several decades of research, many details about the mechanism of ion transport by ClC proteins are not well understood at the molecular level. Our recent quantum calculations[1,2] revealed significant charge delocalization in Cl- binding, which contributes significantly to the effectiveness of the broken helical structure of the binding sites to coordinate Cl- ions. The marked loss of partial charges of the Cl- ions to the surroundings, especially to the residues having π bonds, may impact Cl- transport. Here we report a molecular dynamics study of the movement of Cl- through Escherichia coli ClC where we compare the free energy profiles obtained by employing both the molecular mechanics (MM) and combined quantum mechanics/molecular mechanics (QM/MM) methods.[1] Smith, M.; Lin, H. Chem. Phys. Lett. 2011, 502, 112-117.[2] Church, J.; Pezeshki, S.; Davis, C.; Lin, H. J. Phys. Chem. B 2013, 117, 16029-16043.Acknowledgments: This project is supported by the NSF (CHE-0952337), XSEDE (CHE-140070), and Camille and Henry Dreyfus Foundation (TH-14-028). CD is grateful for the support of the Undergraduate Research Opportunity Program of the University of Colorado Denver.