Systematic coarse-graining of a multicomponent lipid bilayer.

Area of Science:

• Computational chemistry
• Biophysics
• Materials science

Background:

• Developing accurate coarse-grained (CG) models is crucial for simulating complex biological systems like lipid bilayers.
• Existing methods often face challenges with computational efficiency and memory requirements.
• Understanding lipid mixtures is key to comprehending membrane function and phase behavior.

Purpose of the Study:

• To develop a solvent-free CG model for a 1:1 mixed dioleoylphosphatidylcholine (DOPC) and dioleoylphospatidylethanolamine (DOPE) bilayer.
• To enhance the computational efficiency and reduce memory usage of the multiscale coarse-graining (MS-CG) method.
• To investigate the phase behavior and lipid distribution in mixed bilayers.

Main Methods:

• Utilized the multiscale coarse-graining (MS-CG) approach to develop a solvent-free CG model.
• Implemented B-spline basis functions instead of cubic splines within the MS-CG method.
• Validated the CG model by comparing simulation results with all-atom simulations and experimental data.

Main Results:

• The B-spline implementation significantly reduced memory requirements and increased computational efficiency.
• The CG model accurately reproduced structural properties compared to all-atom simulations.
• Simulations revealed fast lipid lateral diffusion and identified small clusters of distinct lipid compositions, indicating nonuniform distribution in the mixed bilayer.

Conclusions:

• The developed MS-CG force field effectively approximates the many-body potential of mean force.
• The enhanced computational efficiency enables the study of lipid phase behavior in binary mixtures.
• The findings suggest a nonuniform lipid distribution in DOPC/DOPE bilayers, consistent with experimental observations.