Substantial progress has been made in the design of protein structure. Observations from natural proteins and mutagenesis experiments, as well as learning from failed protein design attempts, have guided our current understanding. As these examples illustrate, the iteration between computational design and experimental validation is crucial toward improving our models. The approximations necessary for speed in protein design come at the expense of accuracy, and methods for circumventing these limitations will no doubt continue to be improved and invented. Design of protein structure remains challenging: Though some solutions have been found, few guarantees of success currently exist.

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