Тип публикации: статья из журнала

Год издания: 2022

Идентификатор DOI: 10.1126/science.abn2100

Аннотация: <jats:p>The binding and catalytic functions of proteins are generally mediated by a small number of functional residues held in place by the overall protein structure. Here, we describe deep learning approaches for scaffolding such functional sites without needing to prespecify the fold or secondary structure of the scaffold. The fПоказать полностьюirst approach, “constrained hallucination,” optimizes sequences such that their predicted structures contain the desired functional site. The second approach, “inpainting,” starts from the functional site and fills in additional sequence and structure to create a viable protein scaffold in a single forward pass through a specifically trained RoseTTAFold network. We use these two methods to design candidate immunogens, receptor traps, metalloproteins, enzymes, and protein-binding proteins and validate the designs using a combination of in silico and experimental tests.</jats:p>

Журнал: Science

Выпуск журнала: Т. 377, № 6604

Номера страниц: 387-394

ISSN журнала: 00368075

Издатель: American Association for the Advancement of Science

• Wang Jue (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Lisanza Sidney (Graduate Program in Biological Physics, Structure and Design, University of Washington, Seattle, WA 98105, USA.)
• Juergens David (Molecular Engineering Graduate Program, University of Washington, Seattle, WA 98105, USA.)
• Tischer Doug (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Watson Joseph L. (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Castro Karla M. (Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.)
• Ragotte Robert (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Saragovi Amijai (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Milles Lukas F. (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Baek Minkyung (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Anishchenko Ivan (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Yang Wei (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Hicks Derrick R. (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Expòsit Marc (Molecular Engineering Graduate Program, University of Washington, Seattle, WA 98105, USA.)
• Schlichthaerle Thomas (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Chun Jung-Ho (Graduate Program in Biological Physics, Structure and Design, University of Washington, Seattle, WA 98105, USA.)
• Dauparas Justas (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Bennett Nathaniel (Molecular Engineering Graduate Program, University of Washington, Seattle, WA 98105, USA.)
• Wicky Basile I. M. (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Muenks Andrew (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• DiMaio Frank (Institute for Protein Design, University of Washington, Seattle, WA 98105, USA.)
• Correia Bruno (Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.)
• Ovchinnikov Sergey (John Harvard Distinguished Science Fellowship Program, Harvard University, Cambridge, MA 02138, USA.)
• Baker David (Howard Hughes Medical Institute, University of Washington, Seattle, WA 98105, USA.)

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