Crystallization is a highly precise form of molecular self-organization. Protein crystals, in particular have catalytic and materials applications and are central to e?orts in structural biology and therapeutic development. Here, we present a computational approach for the de novo design of protein exteriors and protein-protein interactions so as to arrive at sequences that crystallize into a predetermined crystalline lattice. To verify this approach, a protein is designed de novo to form a polar, layered three-dimensional crystal. For an ensemble of protein orientations consistent with the targeted crystalline structure the sequence-structure energy landscape is characterized using computational protein design. Candidate proteins are identi?ed from minima on this energy landscape. A resulting 2.1 � resolution x-ray crystal structure reveals that one such structure exhibits sub-angstrom agreement with the computational model. This approach should be widely applicable to the design of a variety of crystalline protein architectures.

Computational design of a protein crystal

244th National Meeting (2012)

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