United Atom Lipid Parameters for Combination with the Optimized Potentials for Liquid Simulations All-Atom Force...

Area of Science:

• Computational chemistry
• Biophysics
• Molecular dynamics simulations

Background:

• Accurate molecular dynamics simulations require precise force fields for lipids and proteins.
• Existing force fields for dipalmitoylphosphatidylcholine (DPPC) lipid bilayers have limitations when combined with protein force fields like OPLS-AA.
• Simulations of peptide-lipid interactions are crucial for understanding membrane protein function but are hindered by parameterization challenges.

Purpose of the Study:

• To develop a new united-atom force field for DPPC lipid bilayers compatible with the OPLS-AA protein force field.
• To improve the accuracy of molecular simulations involving lipid bilayers and embedded peptides.
• To enable reliable microsecond-scale simulations of peptide partitioning into lipid membranes.

Main Methods:

• Refitting all torsion parameters with a nonbonded 1-4 scale factor of 0.5.
• Optimizing van der Waals parameters for acyl lipid tails using pentadecane simulations against experimental data.
• Adjusting the charge set for consistent treatment of alkoxy ester groups.

Main Results:

• Simulations of DPPC bilayers at 50 °C yielded an area per lipid of 62.9 ± 0.1 Å(2), closely matching experimental values (63.0 Å(2)).
• Electron density profiles and deuterium order parameters were accurately reproduced.
• The new force field parameters demonstrate improved performance for DPPC bilayers compared to previous models.

Conclusions:

• The developed united-atom lipid force field parameters offer enhanced accuracy for DPPC bilayers.
• This new parameter set facilitates more reliable simulations of peptide-lipid interactions.
• The improved model addresses previous limitations in microsecond-scale peptide partitioning simulations.