Competition between Phase Separation and Micellization in a Coarse-Grained Protein Model with Two Components

Sammanfattning: Intrinsically disordered proteins (IDPs) are widely believed to play a key role in the for- mation of intracellular biomolecular condensates through liquid-liquid phase separation (LLPS). Furthermore, it has been shown in vitro that several IDPs are able to phase sepa- rate on their own. Computational modeling offers unique opportunities to investigate the driving forces and sequence-dependence of IDP LLPS. Prior computational studies have mainly focused on one-component systems. In this thesis, using a coarse-grained model, we investigate the aggregation behavior of systems composed of two hydrophobic/polar sequences, called A and B. On their own, sequence A forms droplets of a dense bulk phase, whereas sequence B forms micellar aggregates. Using Monte Carlo simulations, we in- vestigate the competition between these two aggregation mechanisms in mixed systems containing both sequences. Keeping the total number of chains fixed, we monitor the transition from sequence A-dominated droplet formation to sequence B-dominated micel- lization as the fraction of sequence B chains is increased. The transition entails major changes in both internal organization and size of the observed aggregates, and we find that a variety of intermediate species exist.