Human aquaporin 4 gating dynamics under axially oriented electric-field impulses: A non-equilibrium...

Area of Science:

• Biophysics
• Computational Biology
• Membrane Transport

Background:

• Aquaporins (AQPs) are integral membrane proteins facilitating water transport.
• Human aquaporin 4 (AQP4) is crucial for water homeostasis in various tissues.
• Understanding AQP4's response to external stimuli is vital for physiological and pathological insights.

Purpose of the Study:

• To investigate the effect of external electric fields on human aquaporin 4.
• To analyze water diffusivity and residue dipolar response within AQP4 channels under electric fields.
• To elucidate AQP4's water transport mechanisms under non-equilibrium conditions.

Main Methods:

• Non-equilibrium molecular dynamics (MD) simulations were employed.
• Simulations were conducted with and without pulsed external electric fields (100 ns duration, 0.005-0.015 V/Å intensity).
• Water diffusivity and residue dynamics along the pore axis were analyzed.

Main Results:

• Axially oriented electric fields showed minimal direct impact on overall water permeability.
• Significant spatial variations in water diffusivity were observed, influenced by electric field intensity.
• Residues HIS 201, HIS 95, and ILE 93 were notably affected, enhancing diffusivity at pore mouths.
• Electric fields promoted more uniform water diffusivity within the channel, particularly via selectivity filter manipulation.

Conclusions:

• External electric fields can subtly modulate AQP4 water transport dynamics.
• Specific residue interactions with electric fields are key to altered diffusivity patterns.
• Findings suggest potential for electric field-based regulation of water transport through AQP4.