Fig. 2.

Diagram of computational protocols and strategies. (A) Flowchart of Rosetta computational process showing the multi-step, iterative nature of the Rosetta design and scoring procedures. Only models that achieve specified minimum energies are accepted and output. (B) Schematic of design protocol. At each cycle, starting structures are used to create a large number of designs, which then undergo filtering before being carried to the next cycle. In each of the five cycles, the sampling density is increased by reducing the design perturbation parameters. After the final round of design, the output models are manually assessed to determine the best overall candidate designs.