Dynamic Density Functional Theory of Multicomponent Cellular Membranes

The authors present a continuum model trained on molecular dynamics (MD) simulations for cellular membranes composed of an arbitrary number of lipid types. The authors constructed the model within the formalism of dynamic density functional theory. The community can extend the model to include features such as the presence of proteins and membrane deformations. This framework represents a paradigm shift by enabling simulations that can access length scales on the order of microns and time scales on the order of seconds, all while maintaining near fidelity to the underlying MD models. These length and time scales are significant for accessing biological processes associated with signaling pathways within cells. The authors considered, as an application, membrane interactions with RAS, a protein implicated in roughly 30% of human cancers. The authors presented and verified simulation results with MD simulations, and discussed implications of this new capability.