A top-down and bottom-up combined strategy for parameterization of coarse-grained force fields for phospholipids
Mingwei Wan1,2, Junjie Song2, Ying Yang2
1Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China. fangwh@bnu.edu.cn.
Physical Chemistry Chemical Physics : PCCP
|February 15, 2023
Summary
This study introduces a new method to improve coarse-grained molecular dynamics simulations for phospholipids. The enhanced force field accurately predicts lipid behavior and membrane properties.
Area of Science:
- Computational Chemistry
- Biophysics
- Materials Science
Background:
- Coarse-grained (CG) molecular dynamics (MD) simulations offer insights into molecular assembly and behavior but often lack accuracy.
- Inadequate parameterization of cross-term interactions between CG beads is a key limitation.
Purpose of the Study:
- To develop a novel, accurate, and transferable coarse-grained force field for zwitterionic phospholipids.
- To address the challenge of parameterizing both self- and cross-term interactions in CG models.
Main Methods:
- A combined top-down and bottom-up strategy was employed for force field parameterization.
- Piecewise Morse potential was used for nonbonded van der Waals interactions.
- Top-down optimization matched experimental data (density, heat of vaporization, surface tension).
- Bottom-up optimization fitted pseudo-properties from atomistic simulations (mixing density, intermolecular energy, radial distribution).
Main Results:
- The developed CG force field accurately reproduces structural and thermodynamic properties of lipid membranes in both liquid and gel phases.
- The force field successfully depicts vesicle self-assembly and fusion processes.
- The method demonstrates improved accuracy and transferability of CG force fields.
Conclusions:
- The proposed combined parameterization strategy significantly enhances the accuracy and transferability of CG force fields for phospholipids.
- Matching pseudo-properties from atomistic simulations provides a viable route for developing more reliable CG models.
- This work offers a new approach for accurate simulation of complex lipid systems.
