Abstract
Protein Language Models (PLMs), pre-trained on extensive evolutionary data from natural proteins, have emerged as indispensable tools for protein design. While powerful, PLMs often struggle to produce proteins with precisely specified functionalities or properties due to inherent challenges in controlling their outputs. In this work, we investigate the potential of Activation Steering, a technique originally developed for controlling text generation in Large Language Models (LLMs), to direct PLMs toward generating protein sequences with targeted properties. We propose a simple yet effective method that employs activation editing to steer PLM outputs, and extend this approach to protein optimization through a novel editing site identification module. Through comprehensive experiments on lysozyme-like sequence generation and optimization, we demonstrate that our methods can be seamlessly integrated into both auto-encoding and autoregressive PLMs without requiring additional training. These results highlight a promising direction for precise protein engineering using foundation models. Code is available at https://github.com/Long-Kai/Steering-PLMs.
| Original language | English |
|---|---|
| Title of host publication | Proceedings of the 42nd International Conference on Machine Learning, ICML 2025 |
| Editors | Aarti Singh, Maryam Fazel, Daniel Hsu, Simon Lacoste-Julien, Felix Berkenkamp, Tegan Maharaj, Kiri Wagstaff, Jerry Zhu |
| Publisher | ML Research Press |
| Pages | 26247-26260 |
| Number of pages | 14 |
| Volume | 267 |
| Publication status | Published - 13 Jul 2025 |
| Event | 42nd International Conference on Machine Learning, ICML 2025 - Vancouver Convention Center, Vancouver, Canada Duration: 13 Jul 2025 → 19 Jul 2025 https://icml.cc/Conferences/2025 (Conference Website) https://icml.cc/virtual/2025/calendar (Conference Calendar) https://proceedings.mlr.press/v267/ (Conference Proceedings) |
Publication series
| Name | Proceedings of the International Conference on Machine Learning |
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| Name | Proceedings of Machine Learning Research |
|---|---|
| Volume | 267 |
| ISSN (Print) | 2640-3498 |
Conference
| Conference | 42nd International Conference on Machine Learning, ICML 2025 |
|---|---|
| Country/Territory | Canada |
| City | Vancouver |
| Period | 13/07/25 → 19/07/25 |
| Internet address |
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UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
User-Defined Keywords
- Protein Engineering
- Protein Language Model
- Steering
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