Molecular Dynamics Investigation of Fluoride Ion Permeation and Mechanism in Fluoride Export Protein Bordetella Pertussis (Bpe)

Microorganisms struggle to survive numerous chemical threats, one of which is fluoride ions to which they developed fluoride channels (Fluc) for exporting fluoride out of their cytoplasm. The crystallographic structure and previous studies have spotted an unusual tetrahedrally coordinated non-transported central sodium cation and highlighted certain conserved polar residues along the Fluc pores. However, the exact coordination number of the central sodium and the mechanism of fluoride permeation in relation to these conserved polar residues remains elusive. In this study, we applied the all-atoms molecular dynamics method on WT Fluc-Bpe (Bordetella pertussis) with single fluoride in its pore and with four fluorides alongside its arginine mutants (R23A and R23K). We investigated the possible hydration of central sodium ion to ascertain its coordination, the role of arginine 23, which is an important conserved polar residue, and the permeation mechanism of fluoride. We found out using the watershell analysis that sodium was anhydrous in the WT Fluc and its mutants but hydrated to form a 5-ligand coordination in WT Fluc systems with single fluoride in Fo and F2 binding sites. The dihedral analysis of arginine 23 revealed that it plays a pivotal role in the stabilization of fluoride ions by electrostatic non-bonded interactions made possible by its guanidinium side chain which undergoes dihedral shift for fluoride permeation and efflux. The mechanism of fluoride export for each protein system under study provides insight into the structural dynamics of Fluc’s important arginine polar residue.