Click it or stick it: Covalent and non-covalent methods for protein-self assembly

Abstract Protein complexes are ubiquitous in living systems and have a range of biotechnological applications. However, building protein structures from scratch can be a difficult and laborious process. Here, we review recent developments in protein self-assembly, including a range of tools for covalent and non-covalent assembly of protein structures with user-defined architectures. Key achievements in covalent protein assembly include the development of systems with fast reaction rates and nM affinities. Non-covalent assembly methods have lagged because of the complexity of natural interactions governing protein assembly; but recent developments have created modular methods that are more broadly applicable. On the horizon, we foresee an increasing role for computational protein design tools as key in cementing the role of applications, as opposed to methodology, as the main driving force of research in this field.