Molecular dynamics (MD) simulations are a practical approach to study processes from a molecular point of view. With simulations, we can study rather simple systems such as bulk water and more complex biological systems such as lipid bilayers and lipid droplets. However, to validate the feasibility of MD, we need force field parameters that allow for an accurate representation of molecular behavior. Triglycerides (TGs) and diacylglycerols (DGs) are two of the most abundant species of neutral lipids in cells, and thus it is crucial to obtain accurate parameters for MD simulations of systems containing those molecules. In this work, we improved the CHARMM36 atomistic parameters for TG and DG via reparameterization, implementing strategies compatible with the force field. Our set of parameters can reproduce key properties of TG and DG in their liquid phase, such as density, surface, and interfacial tension.

This image from our work published in Biophysical Reports represents a biphasic system of TG in water. The interfacial tension of TG was calculated by performing MD simulations on this system, with parameters that were iteratively optimized until our results matched with those obtained from experiments. TG molecules are represented in yellow, and water molecules are shown in cyan. Although TGs are mainly hydrophobic molecules, they have a central hydrophilic glycerol moiety. This results in a peculiar distribution of the molecules in bulk, with the glycerol moiety more exposed to water. To appreciate this, we colored the central carbon of the glycerol moiety in red. While accurate parameters for TG and DG are necessary in biological studies to explore the role of these molecules in energy storage, lipid metabolism, and protein signaling, they can also be used in the food industry and engineering studies to understand the physicochemical properties of oils in water and more complex phases.

More information about our group can be found at https://www.unifr.ch/bio/en/groups/vanni/.

- Pablo Campomanes, Janak Prabhu, Valeria Zoni, and Stefano Vanni