Practical approaches to designing novel protein assemblies

•Recent studies focusing on designing highly ordered protein assemblies are reviewed.•Principles related to the spatial organization of subunits are discussed.•Various approaches to designing novel subunit interactions are discussed.•The opportunities for regulation of assembly offered by each approach are discussed.

Molecular self-assembly offers a means by which sophisticated materials can be constructed with unparalleled precision. Designing self-assembling protein structures is of particular interest as a result of the unique functional capabilities of proteins. Custom-designed protein materials could lead to new possibilities in therapeutics, bioenergy, and materials science. Although the field was long hampered by the challenges involved in designing such complex molecules, novel approaches and computational tools have recently led to remarkable progress. Here we review recent design studies in the context of three fundamental aspects of self-assembling materials: subunit organization, subunit interactions, and regulation of assembly.