Free Energy Calculation of Transmembrane Ion Permeation: Sample with a Single Reaction Coordinate and Analysis along...

Area of Science:

• Computational Chemistry
• Biophysics
• Molecular Dynamics

Background:

• Transmembrane permeation of ions and polar molecules is crucial for biological processes.
• Previous studies utilized complex, high-dimensional free energy calculations due to the intricate nature of permeation pathways.
• Existing methods often require multiple reaction coordinates, increasing computational expense.

Purpose of the Study:

• To develop a simplified, single reaction coordinate for umbrella sampling of water-chain-assisted transmembrane permeation.
• To reduce the computational cost associated with free energy calculations for these processes.
• To establish a general methodology for efficient one-dimensional free energy calculations.

Main Methods:

• Design of a single reaction coordinate to capture key configuration changes during permeation.
• Application of one-dimensional umbrella sampling along the new reaction coordinate.
• Utilizing weighted least-square analysis (Welsam) for accurate free energy calculations via bin-segmentation along the minimum free energy path (MFEP).

Main Results:

• The new reaction coordinate effectively captures the entire permeation process, including lipid bilayer deformation, water chain formation, and ion translocation.
• One-dimensional umbrella sampling along the MFEP provides continuous sample data.
• Accurate calculation of the potential of mean force is achieved using Welsam with bin-segmented data.

Conclusions:

• A novel and efficient single reaction coordinate simplifies the study of water-chain-assisted transmembrane permeation.
• The proposed methodology significantly reduces computational costs for free energy calculations.
• This work provides a general framework for 1D free energy calculations in complex multi-dimensional systems.