From coarse-grained molecular dynamics simulations to continuum models of biomolecular condensation

Abstract

Biomolecular condensation contributes to cellular organization and the regulation of numerous biochemical processes. Capturing its dynamics on large spatio-temporal scales requires a macroscopic model that accurately describes both thermodynamic forces and molecular transport. Here, we investigate the applicability of the Cahn-Hilliard equation for modeling phase-separation dynamics in intrinsically disordered proteins. Using the low-complexity domain of FUS as a model system for biomolecular condensation, we perform coarse-grained molecular dynamics simulations to infer the free-energy functional and mobility coefficient entering the Cahn-Hilliard equation. The resulting continuum model accurately describes the growth of initial concentration fluctuations in the spinodal regime and the subsequent morphological evolution of the concentration fields during coarsening. We find that the free-energy functional is transferable across different stages of phase separation, whereas the mobility is not. During coarsening, we identify two kinetic regimes characterized by distinct mobilities, which persist even when a concentration-dependent mobility is introduced.