Ion permeation, selectivity, and electronic polarization in fluoride channels

Area of Science:

• Structural biology and biophysics
• Molecular dynamics simulations
• Ion channel transport mechanisms

Background:

• Fluoride channels (Flucs) are essential for exporting toxic fluoride ions (F-) from the cytoplasm.
• Previous crystallography and mutagenesis studies identified key residues but did not elucidate the molecular permeation mechanism.
• Understanding F- transport is crucial for cellular homeostasis and has implications for various biological processes.

Purpose of the Study:

• To investigate the molecular mechanism of fluoride permeation through an Escherichia coli Fluc protein.
• To elucidate how Flucs achieve high selectivity for F- ions.
• To determine the role of electronic polarization in F--Fluc interactions.

Main Methods:

• Constant-pH molecular dynamics simulations were employed to model the Fluc protein.
• Free-energy-sampling methods were utilized to analyze the permeation pathway of F-.
• Calculations were performed using both electronically polarizable and standard additive force fields.

Main Results:

• Fluoride ions (F-) permeate the channel readily in their charged form through a non-bonded network.
• High F- selectivity is attributed to hydrogen bonding at the central site and a Coulombic filter at the entrance.
• An electronically polarizable force field yielded significantly more accurate F- permeation rates than a standard additive force field.

Conclusions:

• The study provides a detailed molecular mechanism for F- permeation through Flucs.
• Hydrogen bonding and electrostatic interactions are critical for selective F- transport.
• Electronic polarization plays a vital role in F--Fluc interactions, improving simulation accuracy.