Design of protein-binding proteins from the target structure alone.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
05 2022
Historique:
received: 28 09 2021
accepted: 15 03 2022
pubmed: 26 3 2022
medline: 21 5 2022
entrez: 25 3 2022
Statut: ppublish

Résumé

The design of proteins that bind to a specific site on the surface of a target protein using no information other than the three-dimensional structure of the target remains a challenge

Identifiants

pubmed: 35332283
doi: 10.1038/s41586-022-04654-9
pii: 10.1038/s41586-022-04654-9
pmc: PMC9117152
doi:

Substances chimiques

Amino Acids 0
Carrier Proteins 0
Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

551-560

Subventions

Organisme : United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)
ID : FA8750-17-C-0219
Organisme : NIGMS NIH HHS
ID : P41 GM103393
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150855
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM138396
Pays : United States
Organisme : NIH HHS
ID : S10 OD012289
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : R01AG063845
Organisme : NIH HHS
ID : S10 OD021527
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI140245
Pays : United States
Organisme : United States Department of Defense | Defense Threat Reduction Agency (DTRA)
ID : HDTRA1-16-C-0029
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG063845
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150885
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201700059C
Pays : United States

Informations de copyright

© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Références

Chevalier, A. et al. Massively parallel de novo protein design for targeted therapeutics. Nature 550, 74–79 (2017).
pubmed: 28953867 pmcid: 5802399 doi: 10.1038/nature23912
Strauch, E. M. et al. Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site. Nat. Biotechnol. 35, 667–671 (2017).
pubmed: 28604661 pmcid: 5512607 doi: 10.1038/nbt.3907
Silva, D. A. et al. De novo design of potent and selective mimics of IL-2 and IL-15. Nature 565, 186–191 (2019).
pubmed: 30626941 pmcid: 6521699 doi: 10.1038/s41586-018-0830-7
Baran, D. et al. Principles for computational design of binding antibodies. Proc. Natl Acad. Sci. USA 114, 10900–10905 (2017).
pubmed: 28973872 pmcid: 5642698 doi: 10.1073/pnas.1707171114
Fleishman, S. J. et al. Computational design of proteins targeting the conserved stem region of influenza hemagglutinin. Science 332, 816–821 (2011).
pubmed: 21566186 pmcid: 3164876 doi: 10.1126/science.1202617
Dou, J. et al. De novo design of a fluorescence-activating β-barrel. Nature 561, 485–491 (2018).
pubmed: 30209393 pmcid: 6275156 doi: 10.1038/s41586-018-0509-0
Koga, N. et al. Principles for designing ideal protein structures. Nature 491, 222–227 (2012).
pubmed: 23135467 pmcid: 3705962 doi: 10.1038/nature11600
Linsky, T. et al. Sampling of structure and sequence space of small protein folds. Preprint at bioRxiv https://doi.org/10.1101/2021.03.10.434454 (2021).
Maguire, J. B. et al. Perturbing the energy landscape for improved packing during computational protein design. Proteins 89, 436–449 (2021).
pubmed: 33249652 doi: 10.1002/prot.26030
Rocklin, G. J. et al. Global analysis of protein folding using massively parallel design, synthesis, and testing. Science 357, 168–175 (2017).
pubmed: 28706065 pmcid: 5568797 doi: 10.1126/science.aan0693
Schneidman-Duhovny, D., Inbar, Y., Nussinov, R. & Wolfson, H. J. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res. 33, W363–W367 (2005).
pubmed: 15980490 pmcid: 1160241 doi: 10.1093/nar/gki481
Brunette, T. J. et al. Modular repeat protein sculpting using rigid helical junctions. Proc. Natl Acad. Sci. USA 117, 8870–8875 (2020).
pubmed: 32245816 pmcid: 7183188 doi: 10.1073/pnas.1908768117
Coventry, B. & Baker, D. Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds. PLoS Comp. Biol. 17, e1008061 (2021).
doi: 10.1371/journal.pcbi.1008061
Mackenzie, C. O., Zhou, J. & Grigoryan, G. Tertiary alphabet for the observable protein structural universe. Proc. Natl Acad. Sci. USA 113, E7438–E7447 (2016).
pubmed: 27810958 pmcid: 5127300 doi: 10.1073/pnas.1607178113
Wiesmann, C., Ultsch, M. H., Bass, S. H. & de Vos, A. M. Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor. Nature 401, 184–188 (1999).
pubmed: 10490030 doi: 10.1038/43705
Plotnikov, A. N., Hubbard, S. R., Schlessinger, J. & Mohammadi, M. Crystal structures of two FGF–FGFR complexes reveal the determinants of ligand-receptor specificity. Cell 101, 413–424 (2000).
pubmed: 10830168 doi: 10.1016/S0092-8674(00)80851-X
Garrett, T. P. et al. Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor α. Cell 110, 763–773 (2002).
pubmed: 12297049 doi: 10.1016/S0092-8674(02)00940-6
Shim, A. H. et al. Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex. Proc. Natl Acad. Sci. USA 107, 11307–11312 (2010).
pubmed: 20534510 doi: 10.1073/pnas.1000806107
Croll, T. I. et al. Higher-resolution structure of the human insulin receptor ectodomain: multi-modal inclusion of the insert domain. Structure 24, 469–476 (2016).
pubmed: 26853939 pmcid: 4860004 doi: 10.1016/j.str.2015.12.014
Xu, Y. et al. How ligand binds to the type 1 insulin-like growth factor receptor. Nat. Commun. 9, 821 (2018).
pubmed: 29483580 pmcid: 5826941 doi: 10.1038/s41467-018-03219-7
Barton, W. A. et al. Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2–Tie2 complex. Nat. Struct. Mol. Biol. 13, 524–532 (2006).
pubmed: 16732286 doi: 10.1038/nsmb1101
McElroy, C. A., Dohm, J. A. & Walsh, S. T. Structural and biophysical studies of the human IL-7/IL-7Rα complex. Structure 17, 54–65 (2009).
pubmed: 19141282 pmcid: 2654238 doi: 10.1016/j.str.2008.10.019
Arnett, K. L., Harrison, S. C. & Wiley, D. C. Crystal structure of a human CD3-ε/δ dimer in complex with a UCHT1 single-chain antibody fragment. Proc. Natl Acad. Sci. USA. 101, 16268–16273 (2004).
pubmed: 15534202 pmcid: 528977 doi: 10.1073/pnas.0407359101
Radaev, S. et al. Ternary complex of transforming growth factor-β1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily. J. Biol. Chem. 285, 14806–14814 (2010).
pubmed: 20207738 pmcid: 2863181 doi: 10.1074/jbc.M109.079921
Ekiert, D. C. et al. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 489, 526–532 (2012).
pubmed: 22982990 pmcid: 3538848 doi: 10.1038/nature11414
Gillespie, J. J. et al. Structural insight into how bacteria prevent interference between multiple divergent type IV secretion systems. mBio 6, e01867-15 (2015).
pubmed: 26646013 pmcid: 4676284 doi: 10.1128/mBio.01867-15
Birtalan, S. et al. The intrinsic contributions of tyrosine, serine, glycine and arginine to the affinity and specificity of antibodies. J. Mol. Biol. 377, 1518–1528 (2008).
pubmed: 18336836 doi: 10.1016/j.jmb.2008.01.093
Lemmon, M. A. & Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell 141, 1117–1134 (2010).
pubmed: 20602996 pmcid: 2914105 doi: 10.1016/j.cell.2010.06.011
Markovic, I. & Savvides, S. N. Modulation of signaling mediated by TSLP and IL-7 in inflammation, autoimmune diseases, and cancer. Front. Immunol. 11, 1557 (2020).
pubmed: 32849527 pmcid: 7396566 doi: 10.3389/fimmu.2020.01557
Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. Microbiol. Rev. 56, 152–179 (1992).
pubmed: 1579108 pmcid: 372859 doi: 10.1128/mr.56.1.152-179.1992
Nobusawa, E. et al. Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses. Virology 182, 475–485 (1991).
pubmed: 2024485 doi: 10.1016/0042-6822(91)90588-3
Bullough, P. A., Hughson, F. M., Skehel, J. J. & Wiley, D. C. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371, 37–43 (1994).
pubmed: 8072525 doi: 10.1038/371037a0
Ekiert, D. C. et al. Antibody recognition of a highly conserved influenza virus epitope. Science 324, 246–251 (2009).
pubmed: 19251591 pmcid: 2758658 doi: 10.1126/science.1171491
Corti, D. et al. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333, 850–856 (2011).
pubmed: 21798894 doi: 10.1126/science.1205669
Joyce, M. G. et al. Vaccine-induced antibodies that neutralize group 1 and group 2 influenza A viruses. Cell 166, 609–623 (2016).
pubmed: 27453470 pmcid: 4978566 doi: 10.1016/j.cell.2016.06.043
Kadam, R. U. et al. Potent peptidic fusion inhibitors of influenza virus. Science 358, 496–502 (2017).
pubmed: 28971971 pmcid: 5659926 doi: 10.1126/science.aan0516
van Dongen, M. J. P. et al. A small-molecule fusion inhibitor of influenza virus is orally active in mice. Science 363, eaar6221 (2019).
pubmed: 30846569 pmcid: 6457909 doi: 10.1126/science.aar6221
Cao, L. et al. De novo design of picomolar SARS-CoV-2 miniprotein inhibitors. Science 370, 426–431 (2020).
pubmed: 32907861 pmcid: 7857403 doi: 10.1126/science.abd9909
Case, J. B. et al. Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease. Cell Host Microbe 29, 1151–1161 (2021).
pubmed: 34192518 pmcid: 8221914 doi: 10.1016/j.chom.2021.06.008
Quijano-Rubio, A. et al. De novo design of modular and tunable protein biosensors. Nature 591, 482–487 (2021).
pubmed: 33503651 pmcid: 8074680 doi: 10.1038/s41586-021-03258-z
Frejd, F. Y. & Kim, K. T. Affibody molecules as engineered protein drugs. Exp. Mol. Med. 49, e306 (2017).
pubmed: 28336959 pmcid: 5382565 doi: 10.1038/emm.2017.35
Lim, Y. et al. GC1118, an anti-EGFR antibody with a distinct binding epitope and superior inhibitory activity against high-affinity EGFR ligands. Mol. Cancer Ther. 15, 251–263 (2016).
pubmed: 26586721 doi: 10.1158/1535-7163.MCT-15-0679
Zhang, Y. & Skolnick, J. TM-align: a protein structure alignment algorithm based on the TM-score. Nucleic Acids Res. 33, 2302–2309 (2005).
pubmed: 15849316 pmcid: 1084323 doi: 10.1093/nar/gki524
Silva, D. A., Correia, B. E. & Procko, E. Motif-driven design of protein–protein interfaces. Methods Mol. Biol. 1414, 285–304 (2016).
pubmed: 27094298 doi: 10.1007/978-1-4939-3569-7_17
Leaver-Fay, A. et al. ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. Methods Enzymol. 487, 545–574 (2011).
pubmed: 21187238 pmcid: 4083816 doi: 10.1016/B978-0-12-381270-4.00019-6
Hoover, D. M. & Lubkowski, J. DNAWorks: an automated method for designing oligonucleotides for PCR-based gene synthesis. Nucleic Acids Res. 30, e43 (2002).
pubmed: 12000848 pmcid: 115297 doi: 10.1093/nar/30.10.e43
Benatuil, L., Perez, J. M., Belk, J. & Hsieh, C. M. An improved yeast transformation method for the generation of very large human antibody libraries. Protein Eng.Des. Sel. 23, 155–159 (2010).
pubmed: 20130105 doi: 10.1093/protein/gzq002
Stevens, J. et al. Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 303, 1866–1870 (2004).
pubmed: 14764887 doi: 10.1126/science.1093373
Divine, R. et al. Designed proteins assemble antibodies into modular nanocages. Science 372, eabd9994 (2021).
pubmed: 33795432 pmcid: 8592034 doi: 10.1126/science.abd9994
Xu, Y. et al. Addressing polyspecificity of antibodies selected from an in vitro yeast presentation system: a FACS-based, high-throughput selection and analytical tool. Prot. Eng. Des. Sel. 26, 663–670 (2013).
doi: 10.1093/protein/gzt047
Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307–326 (1997).
pubmed: 27799103 doi: 10.1016/S0076-6879(97)76066-X
McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).
pubmed: 19461840 pmcid: 2483472 doi: 10.1107/S0021889807021206
McCoy, A. J., Grosse-Kunstleve, R. W., Storoni, L. C. & Read, R. J. Likelihood-enhanced fast translation functions. Acta Crystallog. D 61, 458–464 (2005).
Adams, P. D. et al. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D58, 1948–1954 (2002).
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126–2132 (2004).
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010).
doi: 10.1107/S0108767309051496
Wehrman, T. et al. Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors. Neuron 53, 25–38 (2007).
pubmed: 17196528 doi: 10.1016/j.neuron.2006.09.034
Kabsch, W. XDS. Acta Crystallogr. D 66, 125–132 (2010).
doi: 10.1107/S010876731009728X
Legrand, P. XDSME: XDS Made Easier. GitHub https://github.com/legrandp/xdsme (2017)
Evans, P. R. An introduction to data reduction: space-group determination, scaling and intensity statistics. Acta Crystallogr. D 67, 282–292 (2011).
doi: 10.1107/S0108767311099223
Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D 69, 1204–1214 (2013).
Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D 67, 235–242 (2011).
Terwilliger, T. C. et al. Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr. D 64, 61–69 (2008).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D66, 486–501 (2010).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).
doi: 10.1107/S010876731009968X
Echols, N. et al. Graphical tools for macromolecular crystallography in PHENIX. J. Appl. Crystallogr. 45, 581–586 (2012).
pubmed: 22675231 pmcid: 3359726 doi: 10.1107/S0021889812017293
Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D 68, 352–367 (2012).
doi: 10.1107/S0108767312007234
Painter, J. & Merritt, E. A. Optimal description of a protein structure in terms of multiple groups undergoing TLS motion. Acta Crystallogr. D 62, 439–450 (2006).
Headd, J. J. et al. Flexible torsion-angle noncrystallographic symmetry restraints for improved macromolecular structure refinement. Acta Crystallogr. D 70, 1346–1356 (2014).
Karplus, P. A. & Diederichs, K. Linking crystallographic model and data quality. Science 336, 1030–1033 (2012).
pubmed: 22628654 pmcid: 3457925 doi: 10.1126/science.1218231
Morin, A. et al. Collaboration gets the most out of software. eLife 2, e01456 (2013).
pubmed: 24040512 pmcid: 3771563 doi: 10.7554/eLife.01456
Plotnikov, A. N., Schlessinger, J., Hubbard, S. R. & Mohammadi, M. Structural basis for FGF receptor dimerization and activation. Cell 98, 641–650 (1999).
pubmed: 10490103 doi: 10.1016/S0092-8674(00)80051-3
Schlessinger, J. et al. Crystal structure of a ternary FGF–FGFR–heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol. Cell 6, 743–750 (2000).
pubmed: 11030354 doi: 10.1016/S1097-2765(00)00073-3
Kabsch, W. Integration, scaling, space-group assignment and post-refinement. Acta Crystallogr. D 66, 133–144 (2010).
doi: 10.1107/S0108767310004551
Liebschner, D. et al. Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr. D 75, 861–877 (2019).
Williams, C. J. et al. MolProbity: more and better reference data for improved all-atom structure validation. Protein Sci. 27, 293–315 (2018).
pubmed: 29067766 doi: 10.1002/pro.3330
Verstraete, K. et al. Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma. Nat. Commun. 8, 14937 (2017).
pubmed: 28368013 pmcid: 5382266 doi: 10.1038/ncomms14937
BUSTER v.2.10.2 (Global Phasing Ltd., 2016).
Joosten, R. P., Long, F., Murshudov, G. N. & Perrakis, A. The PDB_REDO server for macromolecular structure model optimization. IUCrJ 1, 213–220 (2014).
pubmed: 25075342 pmcid: 4107921 doi: 10.1107/S2052252514009324
Evans, P. Scaling and assessment of data quality. Acta Crystallogr. D 62, 72–82 (2006).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
pubmed: 34265844 pmcid: 8371605 doi: 10.1038/s41586-021-03819-2
Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235–242 (2000).
pubmed: 10592235 pmcid: 102472 doi: 10.1093/nar/28.1.235
Berman, H., Henrick, K. & Nakamura, H. Announcing the worldwide Protein Data Bank. Nat. Struct. Biol. 10, 980 (2003).
pubmed: 14634627 doi: 10.1038/nsb1203-980
Grabowski, M. et al. A public database of macromolecular diffraction experiments. Acta Crystallogr. D 72, 1181–1193 (2016).
Grabowski, M. et al. The Integrated Resource for Reproducibility in Macromolecular Crystallography: experiences of the first four years. Struct. Dyn. 6, 064301 (2019).
pubmed: 31768399 pmcid: 6874509 doi: 10.1063/1.5128672
Hornakova, T. et al. Acute lymphoblastic leukemia-associated JAK1 mutants activate the Janus kinase/STAT pathway via interleukin-9 receptor α homodimers. J. Biol. Chem. 284, 6773–6781 (2009).
pubmed: 19139102 pmcid: 2652315 doi: 10.1074/jbc.M807531200
Zhang, J., Kobert, K., Flouri, T. & Stamatakis, A. PEAR: a fast and accurate Illumina Paired-End reAd mergeR. Bioinformatics 30, 614–620 (2014).
pubmed: 24142950 doi: 10.1093/bioinformatics/btt593
Buchan, D. W. A. & Jones, D. T. The PSIPRED Protein Analysis Workbench: 20 years on. Nucleic Acids Res. 47, W402–W407 (2019).
pubmed: 31251384 pmcid: 6602445 doi: 10.1093/nar/gkz297
Lauer, T. M. et al. Developability index: a rapid in silico tool for the screening of antibody aggregation propensity. J. Pharm. Sci. 101, 102–115 (2012).
pubmed: 21935950 doi: 10.1002/jps.22758

Auteurs

Longxing Cao (L)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Brian Coventry (B)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.
Molecular Engineering Graduate Program, University of Washington, Seattle, WA, USA.

Inna Goreshnik (I)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Buwei Huang (B)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.
Department of Bioengineering, University of Washington, Seattle, WA, USA.

William Sheffler (W)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Joon Sung Park (JS)

Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.

Kevin M Jude (KM)

Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.

Iva Marković (I)

VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Unit for Structural Biology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

Rameshwar U Kadam (RU)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.

Koen H G Verschueren (KHG)

VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Unit for Structural Biology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

Kenneth Verstraete (K)

VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Unit for Structural Biology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

Scott Thomas Russell Walsh (STR)

Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
J.A.M.E.S. Farm, Clarksville, MD, USA.

Nathaniel Bennett (N)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.
Molecular Engineering Graduate Program, University of Washington, Seattle, WA, USA.

Ashish Phal (A)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.

Aerin Yang (A)

Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.

Lisa Kozodoy (L)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Michelle DeWitt (M)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Lora Picton (L)

Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.

Lauren Miller (L)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Eva-Maria Strauch (EM)

Deptartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA.

Nicholas D DeBouver (ND)

UCB Pharma, Bainbridge Island, WA, USA.
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA.

Allison Pires (A)

Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA.
Seattle Children's Center for Global Infectious Disease Research, Seattle, WA, USA.

Asim K Bera (AK)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Samer Halabiya (S)

Department of Electrical and Computer Engineering, University of Washington, Seattle, WA, USA.

Bradley Hammerson (B)

Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA.

Wei Yang (W)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Steffen Bernard (S)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.

Lance Stewart (L)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.

Ian A Wilson (IA)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.

Hannele Ruohola-Baker (H)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.

Joseph Schlessinger (J)

Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.

Sangwon Lee (S)

Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.

Savvas N Savvides (SN)

VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Unit for Structural Biology, Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

K Christopher Garcia (KC)

Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.

David 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.

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