Dynamic Density Functional Theory of Multicomponent Cellular Membranes

We present a continuum model trained on molecular dynamics (MD) simulations for cellular membranes composed of an arbitrary number of lipid types. The model is constructed within the formalism of dynamic density functional theory and can be extended to include features such as the presence of proteins and membrane deformations. This framework has enabled 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 molecular interactions. Such scales are significant for accessing biological processes associated with signaling pathways within cells and experimentally relevant regimes. As applications, we consider the cellular interactions of two membrane proteins of biological interest: RAS-RAF complexes and G protein-coupled receptors (GPCRs), where the former is implicated in roughly 30% of human cancers.