Abstract:Protein condensates, such as nucleoli and nuclear speckles, coexist within cells and play critical roles in regulating cellular functions. While attractive interactions among intrinsically disordered regions (IDRs) have been established as a fundamental mechanism for condensation, the sequence rules that govern the coexistence of compositionally distinct condensates remain unclear. In this study, we introduce a theoretical framework for predicting heteropolymer interactions between IDR sequences, eliminating the need for computationally intensive large-scale simulations [1]. Applying this framework to mixtures of multiple types of IDRs, we identified simple sequence-dependent rules that dictate the coexistence of condensates. Further, using the efficiency of our method, we demonstrate the design of sequences that form new condensates coexisting with predefined ones. These findings offer valuable insights into in vitro studies of biomolecular condensates and potentially inform the design principles for functional condensates.
[1] K. Adachi and K. Kawaguchi, Phys. Rev. X 14, 031011 (2024).