Microsecond molecular dynamics simulations of lipid mixing

Area of Science:

• Membrane biophysics
• Computational chemistry
• Materials science

Background:

• Molecular dynamics (MD) simulations are crucial for studying membrane dynamics.
• Limited timescales and slow lipid diffusion often hinder MD studies of lipid mixing.

Purpose of the Study:

• To investigate lipid mixing dynamics and lateral distribution in complex lipid bilayers.
• To characterize the convergence time scale for all-atom MD simulations of lipid mixing.
• To assess the effect of salt concentration on lipid miscibility and membrane properties.

Main Methods:

• Performed microsecond-long all-atom MD simulations using the Anton supercomputer.
• Simulated mixed bilayers of POPE:POPG (3:1) and POPC:cholesterol (2:1), plus a pure POPC bilayer.
• Investigated POPE:POPG bilayers at varying NaCl concentrations (0, 0.15, 1 M) and measured water permeation.

Main Results:

• POPE:POPG and POPC:cholesterol bilayers demonstrated full miscibility, resembling random mixtures.
• Increased NaCl concentration altered area per lipid, tail order, and lateral diffusion, but not mixing states.
• Higher salt concentration (1 M NaCl) reduced water permeability in POPE:POPG bilayers.

Conclusions:

• Microsecond MD simulations provide a benchmark for assessing simulation convergence in lipid mixing studies.
• Equilibrated lipid bilayer structures serve as valuable starting points for simulating bacterial and mammalian membranes.
• Salt concentration influences membrane physical properties and water transport, with implications for membrane function.