Enhanced Sampling of Phase Transitions in Coarse-Grained Lipid Bilayers.

Area of Science:

• Computational biophysics and materials science.
• Investigating lipid bilayer phase transitions and molecular dynamics.

Background:

• Dipalmitoylphosphatidylcholine (DPPC) bilayers are fundamental to cell membranes.
• Understanding their phase transitions is crucial for membrane biophysics.
• Previous studies often simplified solvent effects, necessitating further investigation.

Purpose of the Study:

• To simulate freezing and melting of DPPC bilayers using explicit (Wet) and implicit (Dry) solvent models.
• To analyze phase transitions using an entropic viewpoint based on statistical temperature.
• To compare system behavior and transition temperatures between Wet and Dry simulations.

Main Methods:

• Coarse-grained MARTINI force fields were employed for simulations.
• Enhanced sampling was achieved using the generalized replica exchange method (gREM).
• Bilayer thickness, area per lipid, and order parameter (P2) were calculated as a function of temperature.

Main Results:

• In Wet systems, lipid and water transitions are coupled, influencing reported transition temperatures (292.4 K for 32 lipids).
• Dry systems (390 lipids) exhibit two-dimensional subphases not seen in Wet systems.
• A novel Dry lipid state with differing leaflet structures was observed; transition temperatures were 333.3 K (390 lipids) and 338 K (32 lipids).

Conclusions:

• The entropic approach effectively reveals finite-size effects in DPPC bilayer simulations.
• Explicit solvent leads to coupled lipid-water transitions, while implicit solvent reveals distinct subphases and novel lipid states.
• Simulation system size impacts results, particularly in Dry systems, necessitating careful consideration for accurate phase transition studies.