Exploring the Role of Interfacial Cation in F Ion Channel using MD Simulation: Application of Computational Chemistry

For many microbes, fluoride ion (F-) is toxic in high concentrations. To resist Ftoxicity, microbes have evolved a resistance mechanism, in which the Fluc channel exports Fions with high selectivity. Fluc has several unique features including a dual topology dimeric architecture. It has been shown that a Na+ ion is located at the interface of the dimer, however, the proposed Na+ is tetrahedrally coordinated while Na+ usually coordinates with 5 or 6 ligands. This study provides details about the role of a tetrahedrally–coordinated sodium ion in the structural stability and aid in identifying the contributing residues in high Fselectivity. We are modeling Fluc with various cations including Mg2+ and Mn4+ to provide a comprehensive comparison of Fluc structural stability and conformational changes. This research proposes an alternate interfacial ion for Fluc and could have larger implications for future study of this channel and other cation-coupled transporters for antimicrobial drug design.