Intrinsically disordered proteins (IDPs) lack stable tertiary structures yet play essential roles in diverse biological processes, ranging from molecular recognition to the formation of membraneless organelles. Many IDPs are prone to form biomolecular condensates via liquid-liquid phase separation (LLPS). While the biological function of biomolecular condensates continues to be an active field of research, the condensation of FLOE1, a protein expressed in seeds of Arabidopsis thaliana , has recently been identified as a critical element in the water-sensitive regulation of seed germination. Like many larger IDPs, FLOE1 is not fully disordered but features small domains with residual structure whose importance for the phase-separation properties of FLOE1 is not well explored. Most simulation models used to study sequence-dependent IDP properties, assume fully disordered peptides. Here, we overcome this limitation by combining the CALVADOS2 coarse-grained model with elastic network models to stabilize regions with residual structure in simulations of FLOE1 across a range of temperatures. Our results provide insights into how residual structure in IDPs influences phase separation-behavior and highlight important residues/domains of FLOE1 relevant for phase separation. Beyond the implications of our work for our understanding of IDPs and their properties in general, a deeper understanding of the molecular function of FLOE1 could guide strategies to optimize seed germination, enhance drought resistance, and ultimately improve food security.
Adomako et al. (2026) studied this question.