Significance: Pneumolysin, a pore-forming toxin of Streptococcus pneumoniae , assembles into rings on cholesterol-containing membranes of host cells. β -hairpins form a barrel-shaped transmembrane β -sheet that perforates the membrane, leading to cell lysis. In atomistic and coarse-grained molecular dynamics simulations, we resolve how pneumolysin docks to cholesterol-rich bilayers and how membrane pores form. Remarkably, pneumolysin rings are just wide enough that pores form even if lipid efflux is blocked, driven by spontaneous buckling of the lipid plug. In a survey of electron microscopy and atomic force microscopy images, we identify key intermediates along both the lipid-efflux and plug-buckling pathways of pore opening.

We present simulations of aqueous polyelectrolyte complexes with new MARTINI models for the charged polymers poly(styrene sulfonate) and poly(diallyldimethylammonium). Our coarse-grained polyelectrolyte models allow us to study large length and long time scales with regard to chemical details and thermodynamic properties. The results are compared to the outcomes of previous atomistic molecular dynamics simulations and verify that electrostatic properties are reproduced by our MARTINI coarse-grained approach with reasonable accuracy. Structural similarity between the atomistic and the coarse-grained results is indicated by a comparison between the pair radial distribution functions and the cumulative number of surrounding particles. Our coarse-grained models are able to quantitatively reproduce previous findings like the correct charge compensation mechanism and a reduced dielectric constant of water. These results can be interpreted as the underlying reason for the stability of polyelectrolyte multilayers and complexes and validate the robustness of the proposed models.

By performing molecular dynamics simulations with up to 132 million coarse-grained particles in half-micron sized boxes, we show that hydrodynamics quantitatively explains the finite-size effects on diffusion of lipids, proteins, and carbon nanotubes in membranes. The resulting Oseen correction allows us to extract infinite-system diffusion coefficients and membrane surface viscosities from membrane simulations despite the logarithmic divergence of apparent diffusivities with increasing box width. The hydrodynamic theory of diffusion applies also to membranes with asymmetric leaflets and embedded proteins, and to a complex plasma-membrane mimetic.

Carbon nanotube porins embedded in lipid membranes are studied by molecular dynamics simulations.