Extension of the iSoLF implicit-solvent coarse-grained model for multicomponent lipid bilayers

Area of Science:

• Computational biophysics
• Molecular dynamics simulations
• Membrane biophysics

Background:

• Coarse-grained (CG) models simplify complex molecular systems for large-scale simulations.
• The original iSoLF (iSoLFv1) model enabled molecular dynamics (MD) simulations of lipid bilayers but had limitations in lipid type and electrostatic treatment.
• Accurate modeling of biological membranes is crucial for understanding cellular processes.

Purpose of the Study:

• To develop an improved coarse-grained model (iSoLFv2) for lipid molecules.
• To enhance the simulation accuracy of lipid bilayers by incorporating explicit electrostatic interactions and expanding lipid diversity.
• To validate the new model's performance in reproducing key membrane properties and phase behaviors.

Main Methods:

• All-atom MD simulations were performed using the CHARMM36 force field and modified TIP3P model for parameterization.
• The multistate Boltzmann Inversion method was employed to parameterize bonded and non-bonded interactions.
• iSoLFv2 was tested for its ability to simulate the phase behavior of lipid mixtures (DOPC/DPPC).

Main Results:

• The iSoLFv2 model successfully reproduces the area per lipid and membrane thickness for various lipid bilayers across three temperatures.
• Simulations using iSoLFv2 showed consistency with other advanced models (Dry Martini, Martini 3) for lipid mixture phase behavior.
• The new model significantly reduces computational requirements compared to existing methods.

Conclusions:

• iSoLFv2 represents a significant advancement in coarse-grained lipid modeling, offering improved accuracy and efficiency.
• The model's ability to capture electrostatic interactions and diverse lipid types makes it suitable for complex biological membrane simulations.
• iSoLFv2 is implemented in the GENESIS MD software, ensuring accessibility for the research community.