The membrane potential and its representation by a constant electric field in computer simulations

Area of Science:

• Computational Biophysics
• Theoretical Chemistry
• Molecular Dynamics Simulations

Background:

• Simulating transmembrane potentials is crucial for understanding protein function in biological membranes.
• Existing methods often struggle to accurately capture the influence of external electric fields on membrane proteins.
• Accurate characterization of free energy landscapes under voltage is essential for drug discovery and protein engineering.

Purpose of the Study:

• To elaborate a theoretical framework for incorporating transmembrane potentials into computer simulations.
• To establish methods for calculating the free energy of membrane proteins subjected to voltage differences.
• To validate the theoretical framework using model systems and a potassium channel fragment.

Main Methods:

• Developed a theoretical framework equating constant external electric fields to infinite baths with voltage differences.
• Utilized statistical mechanical reduction of external system degrees of freedom.
• Formulated three distinct routes (W-route, Q-route, G-route) for free energy characterization.

Main Results:

• Demonstrated equivalence between constant electric fields and voltage-controlled infinite baths.
• Showcased displacement charge as a tracker for net charge flow.
• Successfully applied the W, Q, and G routes to model systems, including an ion crossing a slab and a KvAP channel fragment.

Conclusions:

• The elaborated theoretical framework accurately accounts for transmembrane potentials in simulations.
• The W, Q, and G routes provide robust methods for characterizing protein free energy under voltage.
• This work offers a significant advancement for computational studies of voltage-gated proteins and membrane electrophysiology.