| Home > Publications database > Improved protein binder design using β-pairing targeted RFdiffusion > print |
| 001 | 646221 | ||
| 005 | 20260218211012.0 | ||
| 024 | 7 | _ | |a 10.1038/s41467-025-67866-3 |2 doi |
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| 100 | 1 | _ | |a Sappington, Isaac |0 0000-0002-1073-0643 |b 0 |
| 245 | _ | _ | |a Improved protein binder design using β-pairing targeted RFdiffusion |
| 260 | _ | _ | |a [London] |c 2026 |b Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1771420883_1981152 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Designing proteins that bind with high affinity to hydrophilic protein target sites remains a challenging problem. Here we show that RFdiffusion can be conditioned to generate protein scaffolds that form geometrically matched extended β-sheets with target protein edge β-strands in which polar groups on the target are complemented with hydrogen bonding groups on the design. We use this approach to design binders against edge-strand target sites on KIT, PDGFRɑ, ALK-2, ALK-3, FCRL5, NRP1, and α-CTX, and obtain higher (pM to mid nM) affinities and success rates than unconditioned RFdiffusion. Despite sharing β-strand interactions, designs have high specificity, reflecting the precise customization of interacting β-strand geometry and additional designed binder-target interactions. A binder-KIT co-crystal structure is nearly identical to the design model, confirming the accuracy of the design approach. The ability to robustly generate binders to the hydrophilic interaction surfaces of exposed β-strands considerably increases the range of computational binder design. |
| 536 | _ | _ | |a 6G3 - PETRA III (DESY) (POF4-6G3) |0 G:(DE-HGF)POF4-6G3 |c POF4-6G3 |f POF IV |x 0 |
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| 700 | 1 | _ | |a Toul, Martin |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Lee, David S. |0 0000-0001-6539-4272 |b 2 |
| 700 | 1 | _ | |a Robinson, Stephanie A. |b 3 |
| 700 | 1 | _ | |a Goreshnik, Inna |b 4 |
| 700 | 1 | _ | |a McCurdy, Clara |0 0009-0008-8120-9776 |b 5 |
| 700 | 1 | _ | |a Chan, Tung Ching |b 6 |
| 700 | 1 | _ | |a Buchholz, Nic |b 7 |
| 700 | 1 | _ | |a Huang, Buwei |b 8 |
| 700 | 1 | _ | |a Vafeados, Dionne |0 0000-0002-2560-8907 |b 9 |
| 700 | 1 | _ | |a Garcia-Sanchez, Mariana |0 0009-0002-9194-0251 |b 10 |
| 700 | 1 | _ | |a Roullier, Nicole |0 0009-0004-8430-9538 |b 11 |
| 700 | 1 | _ | |a Glögl, Matthias |b 12 |
| 700 | 1 | _ | |a Kim, Christopher J. |0 0000-0003-4305-0473 |b 13 |
| 700 | 1 | _ | |a Watson, Joseph L. |0 0000-0001-5492-0249 |b 14 |
| 700 | 1 | _ | |a Torres, Susana Vázquez |b 15 |
| 700 | 1 | _ | |a Verschueren, Koen H. G. |b 16 |
| 700 | 1 | _ | |a Verstraete, Kenneth |b 17 |
| 700 | 1 | _ | |a Hinck, Cynthia S. |b 18 |
| 700 | 1 | _ | |a Benard-Valle, Melisa |0 0000-0002-0042-6592 |b 19 |
| 700 | 1 | _ | |a Coventry, Brian |0 0000-0002-6910-6255 |b 20 |
| 700 | 1 | _ | |a Sims, Jeremiah Nelson |0 0000-0002-0479-0367 |b 21 |
| 700 | 1 | _ | |a Ahn, Green |0 0000-0003-4482-2754 |b 22 |
| 700 | 1 | _ | |a Wang, Xinru |b 23 |
| 700 | 1 | _ | |a Hinck, Andrew P. |0 0000-0003-3320-8054 |b 24 |
| 700 | 1 | _ | |a Jenkins, Timothy P. |0 0000-0003-2979-5663 |b 25 |
| 700 | 1 | _ | |a Ruohola-Baker, Hannele |0 0000-0002-5588-4531 |b 26 |
| 700 | 1 | _ | |a Banik, Steven M. |0 0000-0002-0544-6488 |b 27 |
| 700 | 1 | _ | |a Savvides, Savvas N. |b 28 |
| 700 | 1 | _ | |a Baker, David |0 P:(DE-H253)PIP1104266 |b 29 |e Corresponding author |
| 773 | _ | _ | |a 10.1038/s41467-025-67866-3 |g Vol. 17, no. 1, p. 1101 |0 PERI:(DE-600)2553671-0 |n 1 |p 1101 |t Nature Communications |v 17 |y 2026 |x 2041-1723 |
| 856 | 4 | _ | |u https://www.nature.com/articles/s41467-025-67866-3#article-info |
| 856 | 4 | _ | |u https://bib-pubdb1.desy.de/record/646221/files/Improved%20protein%20binder%20design%20using%20beta%20pairing%20targeted%20RFdiffusion.pdf |y OpenAccess |
| 856 | 4 | _ | |u https://bib-pubdb1.desy.de/record/646221/files/Improved%20protein%20binder%20design%20using%20beta%20pairing%20targeted%20RFdiffusion.pdf?subformat=pdfa |x pdfa |y OpenAccess |
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