{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:54:16Z","timestamp":1786496056433,"version":"build-2736575974"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"5","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Center of Competence in Research in Molecular Systems Engineering","award":["182895"],"award-info":[{"award-number":["182895"]}]},{"name":"Swiss NSF","award":["310030_197724"],"award-info":[{"award-number":["310030_197724"]}]},{"name":"French Agence Nationale de la Recherche","award":["ANR-22-CPJ2-0075-01"],"award-info":[{"award-number":["ANR-22-CPJ2-0075-01"]}]},{"name":"ERC Consolidator replacement","award":["724228"],"award-info":[{"award-number":["724228"]}]},{"name":"NovoSTAR program","award":["538383"],"award-info":[{"award-number":["538383"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:p>\n                    The human cell surfaceome, integral to cell communication and disease mechanisms, presents a prime target for therapeutic intervention. De novo protein binder design against these cell surface proteins offers a promising yet underexplored strategy for drug development. However, the vast search space and limited data on natural or competitive binders have historically limited experimental success. In this study, we systematically analyzed the entire human surfaceome, identifying approximately 4,500 targetable sites and introducing potential binding seeds for initiating protein design applications. To validate these seeds, we implemented two experimental approaches (protein scaffolding and peptide cyclization) on three representative targets (FGFR2, IFNAR2, and HER3). Our results revealed a high success rate, showing that\n                    <jats:strike\/>\n                    seeds provide valuable starting points for binder design against our identified targetable sites, as well as the need for constant improvements of computational protein design pipelines utilizing machine learning and physics-based methods. Additionally, we present SURFACE-Bind, an interactive database offering open access to all generated data. The high-throughput computational design methods and target-specific binder seeds established here pave the way for a new generation of targeted therapeutics for the human surfaceome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2506269123","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:58:41Z","timestamp":1769619521000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Mapping targetable sites on the human surfaceome for the design of novel binders"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4080-9216","authenticated-orcid":false,"given":"Petra E. M.","family":"Balbi","sequence":"first","affiliation":[{"name":"Institute of Bioengineering, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0724-7990","authenticated-orcid":false,"given":"Ahmed","family":"Sadek","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-0408","authenticated-orcid":false,"given":"Anthony","family":"Marchand","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta-Yi","family":"Yu","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, AI & Digital Innovation, R&D","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6019-4738","authenticated-orcid":false,"given":"Jovan","family":"Damjanovic","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, AI & Digital Innovation, R&D","place":["Lexington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Georgeon","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Fulle","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, AI & Digital Innovation, R&D","place":["M\u00e5l\u00f8v, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4591-5373","authenticated-orcid":false,"given":"Che","family":"Yang","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, AI & Digital Innovation, R&D","place":["M\u00e5l\u00f8v, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-0650","authenticated-orcid":false,"given":"Hamed","family":"Khakzad","sequence":"additional","affiliation":[{"name":"Centre Inria de l\u2019Universit\u00e9 de Lorraine, LORIA, CNRS","place":["Nancy, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7377-8636","authenticated-orcid":false,"given":"Bruno E.","family":"Correia","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2018.09.020"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808790115"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2102164118"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00579-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04654-9"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2023.10.006"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl2528"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38328-5"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06415-8"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05993-x"},{"key":"e_1_3_4_11_2","unstructured":"H. Khakzad SURFACE-Bind database: Binder-accessible surfaceome analysis. Database. https:\/\/surface-bind.inria.fr. 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