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The past, present and future of de novo protein design.

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Title: The past, present and future of de novo protein design.
Authors: Yang W; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Institute of Bio-Architecture and Bio-Interactions (IBABI), Shenzhen Medical Academy of Research and Translation (SMART), Shenzhen, China., Wang S; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.; Institute for Systems Genetics, NYU Langone Health, New York, NY, USA., Lee GR; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea., Zhang JZ; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Courbet A; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA., Juergens D; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Wang X; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Center for Drug Discovery, Northeastern University, Boston, MA, USA.; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA., Schlichthaerle T; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; TUM School of Natural Sciences, Technical University of Munich, Munich, Germany., Abedi M; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Ragotte R; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., An L; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Kalvet I; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA., Pellock S; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Mihaljevic L; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Glasscock C; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Department of BioSciences, Rice University, Houston, TX, USA., Pillai A; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Broerman A; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Ennist N; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Department of Structural and Molecular Biochemistry, North Carolina State University, Raleigh, NC, USA.; Department of Physics, North Carolina State University, Raleigh, NC, USA., Haefner E; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., McNamara-Bordewick N; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Haydon I; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Stewart L; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Bhardwaj G; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA., Baker D; Department of Biochemistry, University of Washington, Seattle, WA, USA. dabaker@uw.edu.; Institute for Protein Design, University of Washington, Seattle, WA, USA. dabaker@uw.edu.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA. dabaker@uw.edu.
Source: Nature [Nature] 2026 Apr; Vol. 652 (8112), pp. 1139-1152. Date of Electronic Publication: 2026 Apr 29.
Publication Type: Journal Article; Review
Journal Info: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
Database: MEDLINE Ultimate
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  Data: <searchLink fieldCode="AU" term="%22Yang+W%22">Yang W</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Institute of Bio-Architecture and Bio-Interactions (IBABI), Shenzhen Medical Academy of Research and Translation (SMART), Shenzhen, China.<br /><searchLink fieldCode="AU" term="%22Wang+S%22">Wang S</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.; Institute for Systems Genetics, NYU Langone Health, New York, NY, USA.<br /><searchLink fieldCode="AU" term="%22Lee+GR%22">Lee GR</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.; 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Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Center for Drug Discovery, Northeastern University, Boston, MA, USA.; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.<br /><searchLink fieldCode="AU" term="%22Schlichthaerle+T%22">Schlichthaerle T</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; TUM School of Natural Sciences, Technical University of Munich, Munich, Germany.<br /><searchLink fieldCode="AU" term="%22Abedi+M%22">Abedi M</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.<br /><searchLink fieldCode="AU" term="%22Ragotte+R%22">Ragotte R</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22An+L%22">An L</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22Kalvet+I%22">Kalvet I</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22Pellock+S%22">Pellock S</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22Mihaljevic+L%22">Mihaljevic L</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22Glasscock+C%22">Glasscock C</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Department of BioSciences, Rice University, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Pillai+A%22">Pillai A</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22Broerman+A%22">Broerman A</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22Ennist+N%22">Ennist N</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA.; 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Institute for Protein Design, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22Bhardwaj+G%22">Bhardwaj G</searchLink>; Institute for Protein Design, University of Washington, Seattle, WA, USA.; Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.<br /><searchLink fieldCode="AU" term="%22Baker+D%22">Baker D</searchLink>; Department of Biochemistry, University of Washington, Seattle, WA, USA. dabaker@uw.edu.; Institute for Protein Design, University of Washington, Seattle, WA, USA. dabaker@uw.edu.; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA. dabaker@uw.edu.
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