CHARMM all-atom additive force field for sphingomyelin: elucidation of hydrogen bonding and of positive curvature.

The C36 CHARMM lipid force field has been extended to include sphingolipids, via a combination of high-level quantum mechanical calculations on small molecule fragments, and validation by extensive molecular dynamics simulations on N-palmitoyl and N-stearoyl sphingomyelin. NMR data on these two molecules from several studies in bilayers and micelles played a strong role in the development and testing of the force field parameters. Most previous force fields for sphingomyelins were developed before the availability of the detailed NMR data and relied on x-ray diffraction of bilayers alone for the validation; these are shown to be too dense in the bilayer plane based on published chain order parameter data from simulations and experiments.

Membrane-binding mechanism of a peripheral membrane protein through microsecond molecular dynamics simulations.

A homologue oxysterol binding protein of yeast (Osh4) peripherally binds to organelle and plasma membranes and promotes lipid transport and membrane contact. Extensive molecular dynamics simulations of Osh4 are used to characterize the structure and mechanism of protein attachment to various model lipid membranes. A high density of negatively charged lipids (phosphatidylserine and phosphatidylinositol-4,5-biphosphate) or a low density of phosphatidylinositol-4,5-biphosphate results in a single binding conformation consisting of interactions with several loops and a portion of the mouth to the lipid binding pocket.

Update of the cholesterol force field parameters in CHARMM.

A modification of the CHARMM36 lipid force field (C36) for cholesterol, henceforth, called C36c, is reported. A fused ring compound, decalin, was used to model the steroid section of cholesterol. For decalin, C36 inaccurately predicts the heat of vaporization (~10 kJ/mol) and molar volume (~10 cc/mol), but C36c resulted in near perfect comparison with experiment.

Sterol binding and membrane lipid attachment to the Osh4 protein of yeast.

Osh4 is an oxysterol-binding protein homologue found in yeast that is essential for the intracellular transport of sterols and cell life. In this study, molecular dynamics simulations were used to investigate the binding of ergosterol, 25-hydroxycholesterol, and lipid moieties to Osh4. The binding energies between both sterols and Osh4 were dominated by van der Waals interactions with residues within the sterol binding pocket, and were further stabilized by water-mediated interactions with polar residues at the bottom of the binding pocket (W46, Q96, Y97, N165, Q181).