Abstract

Biomolecular condensates are highly multi-component systems in which complex phase behaviour can ensue, including the formation of architectures comprising multiple immiscible condensed phases. Relying solely on physical intuition to manipulate them is difficult because of the complexity of their composition. We address this challenge by developing a computational approach which couples a genetic algorithm to a residue-resolution coarse-grained protein model to design pairs of protein sequences that result in well-separated multilayered condensates. We find that the balance of homo- and heterotypic interaction energies between the two components is important for controlling multiphase organisation, and our approach for designing multilayered condensates achieves this balance of interaction energies by optimising the composition and patterning of the protein sequences.