Accurate prediction of protein structures and interactions using a three-track neural network.

Journal: Science (New York, N.Y.)
PMID: 34282049

Abstract

DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.

Authors

  • Minkyung Baek
    Department of Biochemistry and Institute for Protein Design, University of Washington, Washington, WA, USA.
  • Frank DiMaio
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Ivan Anishchenko
    Computational Biology Program, The University of Kansas, Lawrence, Kansas.
  • Justas Dauparas
    Department of Biochemistry and Institute for Protein Design, University of Washington, Washington, WA, USA.
  • Sergey Ovchinnikov
    Center for Systems Biology, Harvard University, Cambridge, MA 02138, United States.
  • Gyu Rie Lee
    Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
  • Jue Wang
    State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau SAR, China.
  • Qian Cong
    Department of Biochemistry, Seattle, WA 98105, USA.
  • Lisa N Kinch
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • R Dustin Schaeffer
    Department of Biophysics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA.
  • Claudia Millán
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  • Hahnbeom Park
    Department of Biochemistry and Institute for Protein Design, University of Washington, Washington, WA, USA.
  • Carson Adams
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Caleb R Glassman
    Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Andy DeGiovanni
    Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
  • Jose H Pereira
    Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
  • Andria V Rodrigues
    Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
  • Alberdina A van Dijk
    Department of Biochemistry, Focus Area Human Metabolomics, North-West University, 2531 Potchefstroom, South Africa.
  • Ana C Ebrecht
    Department of Biochemistry, Focus Area Human Metabolomics, North-West University, 2531 Potchefstroom, South Africa.
  • Diederik J Opperman
    Department of Biotechnology, University of the Free State, 205 Nelson Mandela Drive, Bloemfontein 9300, South Africa.
  • Theo Sagmeister
    Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria.
  • Christoph Buhlheller
    Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria.
  • Tea Pavkov-Keller
    Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria.
  • Manoj K Rathinaswamy
    Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
  • Udit Dalwadi
    Life Sciences Institute, Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
  • Calvin K Yip
    Life Sciences Institute, Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
  • John E Burke
    Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
  • K Christopher Garcia
    Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Nick V Grishin
    Department of Biophysics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA.
  • Paul D Adams
    Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Randy J Read
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  • David Baker
    Department of Biochemistry, University of Washington, Seattle, Washington.

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