Simulations of lipid bilayers using the CHARMM36 force field with the TIP3P-FB and TIP4P-FB water models.

Fatima Sajadi,Christopher N Rowley

doi:10.7717/peerj.5472

Abstract

The CHARMM36 force field for lipids is widely used in simulations of lipid bilayers. The CHARMM family of force fields were developed for use with the mTIP3P water model. This water model has an anomalously high dielectric constant and low viscosity, which limits its accuracy in the calculation of quantities like permeability coefficients. The TIP3P-FB and TIP4P-FB water models are more accurate in terms of the dielectric constant and transport properties, which could allow more accurate simulations of systems containing water and lipids. To test whether the CHARMM36 lipid force field is compatible with the TIP3P-FB and TIP4P-FB water models, we have performed simulations of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers. The calculated headgroup area, compressibility, order parameters, and X-ray form factors are in good agreement with the experimental values, indicating that these improved water models can be used with the CHARMM36 lipid force field without modification when calculating membrane physical properties. The water permeability predicted by these models is significantly different; the mTIP3P-model diffusion in solution and at the lipid–water interface is anomalously fast due to the spuriously low viscosity of mTIP3P-model water, but the potential of mean force of permeation is higher for the TIP3P-FB and TIP4P-FB models due to their high excess chemical potentials. As a result, the rates of water permeation calculated the FB water models are slower than the experimental value by a factor of 15–17, while simulations with the mTIP3P model only underestimate the water permeability by a factor of 3.

Highlights

Realistic molecular dynamics (MD) simulations of lipid-containing systems like bilayers, vesicles, and membrane–protein systems require accurate molecular mechanical force fields for lipids
We report physical and structural properties of lipid bilayers described using the CHARMM36 lipid model, in combination with the mTIP3P, TIP3P-FB, and TIP4P-FB water models
The headgroup area, compressibility, X-ray and neutron scattering profiles, and acyl-chain deuterium order parameters were compared to experimental values

Summary

Introduction

Realistic molecular dynamics (MD) simulations of lipid-containing systems like bilayers, vesicles, and membrane–protein systems require accurate molecular mechanical force fields for lipids. These models have been carefully parameterized using ab initio data and the empirical properties of bilayers. How to cite this article Sajadi and Rowley (2018), Simulations of lipid bilayers using the CHARMM36 force field with the TIP3P-FB and TIP4P-FB water models. The performance of these models is evaluated based on their ability to predict empirical data regarding the structure and dynamics of lipid properties

Methods

Results

Discussion

Conclusion