In silico discovery of nanobody binders to a G protein coupled receptor using AlphaFold Multimer

Edward P. Harvey^1,* , Jeffrey S. Smith^{1,2, *}, Joseph D. Hurley^1,*, Alyana Granados³, Ernst W. Schmid¹, Jason G. Liang-Lin¹, Huyang Zhang¹, Emily M. Meara^1,2, Elizabeth K. Wren¹, Steffanie Paul^4,5, Matthew P. Ferguson¹, Victor G. Calvillo-Miranda¹, Miguel A. Alcantar^1,6, Debora S. Marks^4,5, Johannes C. Walter^1,7, Andrew C. Kruse^1,†, Katherine J. Susa^3,†

¹Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
²Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, 02115,USA.
³Department of Pharmaceutical Chemistry, University of California, San Francisco, CA94158, USA
⁴Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA
⁵Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA
⁶Department of Biomedical Engineering, University of California, Irvine, CA, 92697, USA
⁷Howard Hughes Medical Institute, Boston, MA, USA
^*These authors contributed equally.
^†Correspondence to: Andrew C. Kruse (Andrew_kruse@hms.harvard.edu) and Katherine J. Susa (Katherine.Susa@ucsf.edu)

• Received02 October 2025
• Accepted03 April 2026
• Published23 April 2026

https://doi.org/10.1038/s41467-026-72093-5