Simulating the proton transfer in gramicidin A by a sequential dynamical Monte Carlo method.

Area of Science:

• Biophysics
• Computational Biology
• Biochemistry

Background:

• Long-range proton transfer is vital for biochemical processes like energy transduction and drug detoxification.
• Simulating proton transfer at the microsecond timescale is challenging for standard molecular methods.
• Master equations describe reactive system dynamics but are computationally demanding due to numerous microstates.

Purpose of the Study:

• To introduce a novel computational method for simulating long-range proton transfer in biomolecules.
• To apply this method to understand proton transfer mechanisms in biological systems.
• To overcome the limitations of existing simulation techniques for microsecond timescale dynamics.

Main Methods:

• Developed a sequential dynamical Monte Carlo algorithm to solve the master equation.
• Used continuum electrostatic calculations to determine energetic parameters for simulations.
• Modeled proton transfer through gramicidin A, including proton uptake/release, hydrogen bond transfer, and water molecule rotations.

Main Results:

• The new method efficiently simulates proton transfer dynamics at microsecond timescales.
• Simulations showed good agreement with experimental data for proton flux through gramicidin A.
• Proton desolvation and water rotations were found to be equally critical for proton transfer at physiological membrane potentials.

Conclusions:

• The developed Monte Carlo method enables simulations of long-range charge transfer in biological systems at previously inaccessible timescales.
• This approach provides valuable insights into the mechanisms of proton transfer in biomolecules.
• The findings highlight the importance of both proton desolvation and water dynamics in transmembrane proton channels.