The CHARMM36 Force Field for Lipids Can Be Used With More Accurate Water Models

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 TIP3P 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 DPPC and POPC 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. The water permeability predicted by these models is significantly different; the TIP3P-model diffusion in solution and at the lipid--water interface is anomalously fast due to the spuriously low viscosity of TIP3P-model water, but the PMF of permeation is higher for the TIP3P-FB and TIP4P-FB models due to their high excess chemical potentials.

The role of structural order in heterogeneous ice nucleation

“…Cholesterol and water molecules were both modelled at the atomistic level via the CHARMM36 force field 42,43 and the TIP4P/Ice 44 model, respectively. This specific combination has been validated on multiple occasions within the recent literature: not only has it been demonstrated to provide an accurate description of supercooled water and ice at the interface with biological material, 45–47 but we have also explicitly verified its reliability for water and ice in contact with cholesterol. 33…”

“…Cholesterol and water molecules were both modelled at the atomistic level via the CHARMM36 force eld 42,43 and the TIP4P/ Ice 44 model, respectively. This specic combination has been validated on multiple occasions within the recent literature: not only has it been demonstrated to provide an accurate description of supercooled water and ice at the interface with biological material, [45][46][47] but we have also explicitly veried its reliability for water and ice in contact with cholesterol. 33 The GROMACS package (version 5.1.4) 42,48 has been used to perform molecular dynamics (MD) simulations within a variety of ensembles, including the NgT ensemble (with constant surface tension g) 49 so as to take into account different CHL coverages (i.e., different values of surface area per molecule, S A / mol).…”