Self-Assembly-Induced Protein Crystallization

Previous work has established that protein clusters formed inside the liquid-liquid coexistence envelope can facilitate crystal nucleation. However, recent experiments have indicated the existence of clustering-induced protein nucleation even "outside" this phase boundary. Here we simulate a minimal model of patchy particles, which are more representative of anisotropic interprotein interactions, and find that transient clusters formed through self-assembly can nucleate crystal growth even under conditions where a dense protein liquid is thermodynamically unstable. The patchy nature of protein interactions thus greatly facilitates their self-assembly, which then "guides" the subsequent crystal morphology.