Calculating Single-Channel Permeability and Conductance from Transition Paths.

Area of Science:

• Biophysics
• Computational Chemistry

Background:

• Membrane channel transport properties like permeability and conductance are vital.
• Calculating these properties via all-atom molecular dynamics simulations is desirable but challenging for low solute crossing rates.

Purpose of the Study:

• To develop a novel, accurate method for calculating solute crossing rates in membrane channels using molecular dynamics simulations.
• To overcome the limitations of direct simulation methods for low crossing rates.

Main Methods:

• Initiating unbiased molecular dynamics trajectories with the solute released at the free energy barrier.
• Utilizing the time spent by the solute in the barrier region (transition path) to determine the kinetic rate.

Main Results:

• The new method achieves significantly higher statistical accuracy than the classical reactive flux method, particularly for diffusive barrier crossing.
• Testing on ion permeation through a carbon nanotube confirmed accurate prediction of crossing rates and spontaneous events.

Conclusions:

• The developed method provides a rigorous and efficient approach for calculating membrane channel crossing rates.
• This technique facilitates quantitative connections between molecular dynamics simulations and experimental measurements of membrane channels.