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Triacylglycerols (TG) are the primary neutral lipids in lipid droplets (LDs), organelles responsible for lipid storage, metabolism, and signaling. Molecular dynamics (MD) simulations have provided valuable insight into LD structure, but fixed-charge force fields struggle to capture TG behavior across both hydrophobic cores and polar interfaces. Here, we develop and evaluate a polarizable TG model using the Drude2023 lipid force field and benchmark its performance against experimental measurements of bulk density, TG−water interfacial tension, core hydration, and monolayer expansion. The Drude model accurately reproduces the experimental properties and captures key monolayer features such as surface-oriented TGs (SURF-TGs) and chemically distinct membrane packing defects. Compared to fixed-charge models such as C36-standard and C36-cutoff, the Drude polarizable model is the only force field able to capture the dual nature of TG at polar−nonpolar interfaces like the LD monolayer and more homogeneous hydrophobic environments, like the LD core. However, C36-standard is consistent with the Drude results for the LD monolayer, while C36-cutoff is consistent with the decreased hydration in the LD core. Even with large applied surface tensions, C36-cutoff does not produce Drude-like LD monolayer properties. These results highlight the importance of dynamic polarizability and establish Drude2023 as a more reliable framework for simulating TG in heterogeneous systems like LDs.
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Characterizing the Water Wire in the Gramicidin Channel Found by Monte Carlo Sampling Using Continuum Electrostatics and in Molecular Dynamics Trajectories with Conventional or Polarizable Force Fields
• Water is the primary cellular solvent, yet is challenging to simulate computationally. Here we simulate water molecules in the Gramicidin A channel comparing Monte Carlo (MC) sampling with a continuum electrostatics and Molecular Dynamics (MD) calculations with the non-polarizable CHARMM36 and polarizable Drude force fields. • These give different water properties, with classical MD yielding well oriented water wires, while the Drude or continuum electrostatics force fields lead to more disordered water molecules, often changing orientation in the middle of the channel.
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- Award ID(s):
- 1855942
- PAR ID:
- 10225739
- Date Published:
- Journal Name:
- Journal of Computational Biophysics and Chemistry
- Volume:
- 20
- Issue:
- 02
- ISSN:
- 2737-4165
- Page Range / eLocation ID:
- 111 to 130
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1142/S2737416520420016
