CHARMM-GUI Membrane Builder for Lipid Droplet Modeling and Simulation

Area of Science:

• Biochemistry
• Molecular Biology
• Computational Biology

Background:

• Lipid droplets (LDs) are vital organelles for energy storage and metabolism in prokaryotes and eukaryotes.
• Their structure, a neutral lipid core within a phospholipid monolayer, is key to their function.
• LDs are implicated in diseases and explored for drug delivery, necessitating advanced study tools.

Purpose of the Study:

• To evaluate CHARMM-GUI Membrane Builder for simulating and analyzing lipid droplet systems.
• To investigate the behavior of triacylglycerol (TAG) within simulated LDs.
• To assess the impact of oleosin, a plant LD protein, on LD structure.

Main Methods:

• Utilized CHARMM-GUI Membrane Builder for all-atom simulations of LDs.
• Employed a new TAG library with optimized headgroup parameters for accurate simulations.
• Simulated LDs with varying TAG mole fractions and in the presence of oleosin.

Main Results:

• Membrane Builder efficiently generated biologically relevant LD systems with short equilibration times.
• Inserted TAG molecules self-assembled into a distinct TAG-only core within the lipid bilayer.
• The TAG core thickness increased with TAG mole fraction, accommodating oleosin at 70% TAG without structural disruption.

Conclusions:

• CHARMM-GUI Membrane Builder is a valuable tool for simulating and analyzing lipid droplet systems.
• The simulation accurately models TAG aggregation and core formation within LDs.
• This approach facilitates future studies on LD structure, dynamics, and protein interactions.