Design of a Novel Globular Protein Fold with Atomic-Level Accuracy
Brian Kuhlman,1* Gautam Dantas,1* Gregory C. Ireton,4 Gabriele Varani,1,2 Barry L. Stoddard,4 David Baker1,3
A major challenge of computational protein design is the creation of novel proteins with arbitrarily chosen three-dimensional structures. Here, we used a general computational strategy that iterates between sequence design and structure prediction to design a 93-residue /ß protein called Top7 with a novel sequence and topology. Top7 was found experimentally to be folded and extremely stable, and the x-ray crystal structure of Top7 is similar (root mean square deviation equals 1.2 angstroms) to the design model. The ability to design a new protein fold makes possible the exploration of the large regions of the protein universe not yet observed in nature.
1 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
2 Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
3 Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
4 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
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