Biomolecular simulations with the transferable potentials for phase equilibria: extension to phospholipids

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Biophysics

Background:

• Accurate molecular force fields are crucial for simulating biological systems.
• Existing force fields may not adequately represent charged or zwitterionic lipid head groups.
• Lipid bilayers are fundamental components of cell membranes.

Purpose of the Study:

• To extend the Transferable Potentials for Phase Equilibria (TraPPE) force field to include zwitterionic and charged lipids.
• To validate the performance of the extended TraPPE force field for hydrated lipid bilayers.
• To assess the impact of water models and ion parameters on lipid force field accuracy.

Main Methods:

• Isothermal-isobaric ensemble (NPT) molecular dynamics simulations were performed.
• Simulations included various lipid head groups (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol) and alkyl tails (C12-C18, saturated and unsaturated).
• The effects of different water models and sodium ion parameters were investigated.

Main Results:

• The extended TraPPE force field accurately predicts area per lipid, bilayer thickness, and volume per lipid (within 1-5% of experimental values).
• Simulated structural properties, including sn-2 chain order parameter splitting and X-ray form factors, closely match experimental data.
• The force field's performance is validated across a range of lipid types and tail compositions.

Conclusions:

• The extended TraPPE force field provides a reliable tool for simulating zwitterionic and charged lipid bilayers.
• This advancement enables more accurate computational studies of membrane biophysics and lipid-protein interactions.
• The validated force field contributes to a deeper understanding of cell membrane structure and function.