35TL

PD-L1 complexed with Germinal-designed anti-PD-L1 scFv H5

Summary for 35TL

• Entry DOI: 10.2210/pdb35tl/pdb
• EMDB information: 77181
• Descriptor: Programmed cell death 1 ligand 1, Germinal-designed anti-PD-L1 scFv H5, V(H) domain, Germinal-designed anti-PD-L1 scFv H5, V(L) domain (3 entities in total)
• Functional Keywords: scfv, designed, binder, de novo protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 80603.39

Authors

Zhang, J.L.,Rao, B.,Feng, L. (deposition date: 2026-05-15, release date: 2026-07-22)

Primary citation

Mille-Fragoso, L.S.,Driscoll, C.L.,Wang, J.N.,Dai, H.,Widatalla, T.,Zhang, J.L.,Zhang, X.,Rao, B.,Feng, L.,Hie, B.L.,Gao, X.J.
Efficient generation of epitope-targeted antibodies with Germinal.
Nat.Biotechnol., 2026

PubMed Abstract: Obtaining antibodies to specific protein targets is a widely important yet experimentally laborious process. Meanwhile, computational methods for antibody design have been limited by low success rates that require resource-intensive screening. Here we introduce Germinal, a broadly enabling generative pipeline that designs antibodies against specific epitopes with nanomolar binding affinities while requiring only low-n experimental testing. Our method co-optimizes antibody structure and sequence by integrating a structure predictor with an antibody-specific protein language model to perform de novo design of functional complementarity-determining regions onto a user-specified structural framework. When tested against four diverse protein targets, Germinal designed functional antibodies across all targets and binder formats, testing only 43-101 designs for each antigen. Validated designs also exhibited robust expression in mammalian cells and high sequence and structural novelty. We provide open-source code and full computational and experimental protocols to facilitate wide adoption.

PubMed: 42337361
DOI: 10.1038/s41587-026-03187-0

Experimental method

ELECTRON MICROSCOPY (3.93 Å)