A Polarizable Atomic Multipole-Based Force Field for Molecular Dynamics Simulations of Anionic Lipids

Area of Science:

• Computational Chemistry
• Biomolecular Simulation
• Force Field Development

Background:

• Classical force fields often neglect electronic polarizability, simplifying electrostatic interactions.
• Condensed-phase polarization is typically approximated by fixed, increased atomic charges.
• Developing accurate polarizable force fields is essential for realistic biomolecular simulations.

Purpose of the Study:

• To extend the Atomic Multipole Optimized Energetics for BiomoleculAr (AMOEBA) polarizable force field to include new anionic lipids: DMPG and POPS.
• To develop and validate new force field parameters for simulating anionic lipid bilayers.
• To improve the representation of electrostatic interactions and polarization in lipid simulations.

Main Methods:

• Developed new anionic lipid models (DMPG, POPS) within the AMOEBA force field framework.
• Utilized ab initio gas-phase calculations to derive atomic multipole moments (monopole, dipole, quadrupole).
• Performed molecular dynamics simulations of DMPG and POPS membrane bilayers with explicit water.

Main Results:

• The new force field parameters were validated through simulations of DMPG and POPS bilayers.
• Calculated properties include membrane width, area per lipid, and deuterium order parameters.
• Key bilayer characteristics were compared with available experimental data.

Conclusions:

• The developed force field parameters provide a more accurate representation of electrostatic interactions and polarization for anionic lipids.
• These parameters are compatible with the existing AMOEBA force field, enabling simulations of complex biological systems.
• The study validates the use of polarizable force fields for detailed investigations of anionic lipid membrane properties.