Accurate Simulations of Lipid Monolayers Require a Water Model with Correct Surface Tension.

Carmelo Tempra,O H Samuli Ollila,Matti Javanainen

doi:10.1021/acs.jctc.1c00951

Abstract

Lipid monolayers provide our lungs and eyes their functionality and serve as proxy systems in biomembrane research. Therefore, lipid monolayers have been studied intensively including using molecular dynamics simulations, which are able to probe their lateral structure and interactions with, e.g., pharmaceuticals or nanoparticles. However, such simulations have struggled in describing the forces at the air–water interface. Particularly, the surface tension of water and long-range van der Waals interactions have been considered critical, but their importance in monolayer simulations has been evaluated only separately. Here, we combine the recent C36/LJ-PME lipid force field that includes long-range van der Waals forces with water models that reproduce experimental surface tensions to elucidate the importance of these contributions in monolayer simulations. Our results suggest that a water model with correct surface tension is necessary to reproduce experimental surface pressure–area isotherms and monolayer phase behavior. The latter includes the liquid expanded and liquid condensed phases, their coexistence, and the opening of pores at the correct area per lipid upon expansion. Despite these improvements of the C36/LJ-PME with certain water models, the standard cutoff-based CHARMM36 lipid model with the 4-point OPC water model still provides the best agreement with experiments. Our results emphasize the importance of using high-quality water models in applications and parameter development in molecular dynamics simulations of biomolecules.

Highlights

Monolayers of amphiphilic lipids serve as a proxy for lipid membranes in studies of membrane structure and membrane− protein interactions[1,2] since they are significantly more straightforward to study with a wide range of spectroscopic and microscopic methods as compared to lipid bilayers.[3,4] lipid monolayers form functionally essential structures that line the alveoli in the lungs and cover the surfaces of the eyes.[5]
We have recently demonstrated that the CHARMM36 (“C36” on) lipid model[13] combined with the 4-point OPC water model (“OPC4” on)[18] provides nearly quantitative agreement with experimental surface pressure− area isotherms of both single-component[15] and multicomponent[19] lipid monolayers
As explained in the Methods section, the conversion of C36/ LJ-PME force field parameters from CHARMM to GROMACS format was accurate, but small deviations in nonbonded single point energies between GROMACS and OpenMM probably arise from implementation details of LJ-PME

Summary

Introduction

Monolayers of amphiphilic lipids serve as a proxy for lipid membranes in studies of membrane structure and membrane− protein interactions[1,2] since they are significantly more straightforward to study with a wide range of spectroscopic and microscopic methods as compared to lipid bilayers.[3,4] lipid monolayers form functionally essential structures that line the alveoli in the lungs and cover the surfaces of the eyes.[5] In the lungs, a pulmonary surfactant (PS) monolayer covers the alveolar liquid, preventing the collapse of the alveoli during exhalation. A tear film lipid layer (TFLL) consists of a monolayer that separates the tear fluid from the nonpolar wax layer of the TFLL, helping the latter spread rapidly between eye blinks. This behavior depends on the subtle balance of forces at the liquid− air interface

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Methods

Results

Conclusion