Starkly Speaking: Efficient generation of epitope-targeted de novo antibodies with Germinal
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Hannes Stärk
Nov 24, 2025, 6:51:26 AM11/24/25
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Hi together,
In todays reading group session in around 5h we will discuss:
Speaker:
Talal Widatalla and Claudia L. Driscoll from Stanford and Arc Institute.
Paper:
Efficient generation of epitope-targeted de novo antibodies with Germinal https://www.biorxiv.org/content/10.1101/2025.09.19.677421v2 (Luis S. Mille-Fragoso, John N. Wang, Claudia L. Driscoll, Haoyu Dai, Talal Widatalla, Xiaowei Zhang, Brian L. Hie, and Xiaojing J. Gao)
Obtaining novel antibodies against 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 currently require resource-intensive screening. Here, we introduce Germinal, a broadly enabling generative framework 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 (CDRs) onto a user-specified structural framework. When tested against four diverse protein targets, Germinal achieved an experimental success rate of 4-22% across all targets, testing only 43-101 designs for each antigen. Validated nanobodies also exhibited robust expression in mammalian cells and nanomolar binding affinities. We provide open-source code and full computational and experimental protocols to facilitate wide adoption. Germinal represents a milestone in efficient, epitope-targeted de novo antibody design, with notable implications for the development of molecular tools and therapeutics.
Meeting Details:
Every Monday at 9:00 PT / 12:00 ET / 18:00 CE(S)T
https://zoom.us/j/5775722530?pwd=ZzlGTXlDNThhUDZOdU4vN2JRMm5pQT09
Slack Workspace for discussion and paper voting:
https://join.slack.com/t/logag/shared_invite/zt-2zuxi7gd1-rLUgxg6gnCkhO7WlRsyElg
All information: Schedule of upcoming papers, recordings, mailing list:
https://portal.valencelabs.com/starklyspeaking
Speaker:
Talal Widatalla and Claudia L. Driscoll from Stanford and Arc Institute.
Paper:
Efficient generation of epitope-targeted de novo antibodies with Germinal https://www.biorxiv.org/content/10.1101/2025.09.19.677421v2 (Luis S. Mille-Fragoso, John N. Wang, Claudia L. Driscoll, Haoyu Dai, Talal Widatalla, Xiaowei Zhang, Brian L. Hie, and Xiaojing J. Gao)
Obtaining novel antibodies against 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 currently require resource-intensive screening. Here, we introduce Germinal, a broadly enabling generative framework 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 (CDRs) onto a user-specified structural framework. When tested against four diverse protein targets, Germinal achieved an experimental success rate of 4-22% across all targets, testing only 43-101 designs for each antigen. Validated nanobodies also exhibited robust expression in mammalian cells and nanomolar binding affinities. We provide open-source code and full computational and experimental protocols to facilitate wide adoption. Germinal represents a milestone in efficient, epitope-targeted de novo antibody design, with notable implications for the development of molecular tools and therapeutics.
Meeting Details:
Every Monday at 9:00 PT / 12:00 ET / 18:00 CE(S)T
https://zoom.us/j/5775722530?pwd=ZzlGTXlDNThhUDZOdU4vN2JRMm5pQT09
Slack Workspace for discussion and paper voting:
https://join.slack.com/t/logag/shared_invite/zt-2zuxi7gd1-rLUgxg6gnCkhO7WlRsyElg
All information: Schedule of upcoming papers, recordings, mailing list:
https://portal.valencelabs.com/starklyspeaking
Hannes Stärk
Website: https://hannes-stark.com
PhD student at MIT
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