Study of trioleoylglycerol two-layer and adiposome cross-section mimicking four-layer systems through atomic-level simulations.

Adiposomes are artificially prepared lipid droplet (LD)-mimetic structures, which, unlike LDs, do not harbor proteins. The dynamics of interaction between triacylglycerols (TAGs), drug molecule, and phospholipids in adiposomes is currently not well-established. Trioleoylglycerol (TOG) molecule was divided into three parts: two oleoyl tails and one 2-monooleoylglycerol (MOG). Forcefield parameters for two oleoyl tails were adopted from the AMBER18 repository while that of the MOG forcefield was taken from the literature. Charge correction was performed on the MOG forcefield before its utilization. After charge correction, the resulting TOG molecule had zero charge. TOG bilayer (2L) and tetralayer (4L) systems were prepared and simulated. TOG bilayer (2L) systems-modeled from two different initial conformations, the TOG3 conformation and the TOG2:1 conformation-showed that TOG2:1 conformation was more prevailing irrespective of the starting conformation and was subsequently used in further simulations. The hydrated TOG 2L system showed TOG-water solution solubility of 0.051 mol L^-1 which is near experimental values. This validated the correct parameterization of the TOG molecule. The simulations of 4L systems showed stable membrane behaviors toward the end of simulations. It was also observed that in the 4L system, the TOG molecules showed the formation of micelles with the drug molecule. Almost six TOGs remained continuously in contact with the drug molecule throughout the simulation. The availability of charge-corrected TOG parameterization is expected to equip future studies with a framework for molecular dynamics simulations of adiposomes and/or LDs at the atomic level.