Density-biased sampling: a robust computational method for studying pore formation in membranes.

Area of Science:

• Computational Chemistry
• Biophysics
• Materials Science

Background:

• Molecular dynamics simulations are crucial for understanding molecular behavior.
• Enhanced sampling techniques are needed to study rare events like phase transitions and membrane dynamics.
• Existing methods may not accurately capture density-driven processes.

Purpose of the Study:

• To introduce a new reaction coordinate for biasing molecular dynamics simulations.
• To enable enhanced sampling of density-driven processes, including mixing and demixing.
• To apply and validate this methodology for studying phospholipid membrane pore formation.

Main Methods:

• Developed a novel reaction coordinate for biasing molecular dynamics.
• Validated the method by calculating the entropy of demixing ideal gas species.
• Applied the biasing potential within an umbrella sampling framework to phospholipid membranes.
• Simulated membrane deformation and pore formation.

Main Results:

• The new reaction coordinate effectively enhances sampling of density-driven processes.
• Theoretical entropy of demixing ideal gases was accurately reproduced.
• Simulations successfully induced deformation and pore formation in phospholipid membranes.
• The density-based biasing potential revealed a more realistic transition pathway compared to previous studies.

Conclusions:

• The described reaction coordinate is a powerful tool for enhanced sampling in molecular dynamics.
• This method provides a more accurate representation of transition pathways in complex systems like lipid membranes.
• The approach has significant implications for studying phenomena driven by density changes.