Steering Protein Language Models
About
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.
Related benchmarks
| Task | Dataset | Result | Rank | |
|---|---|---|---|---|
| Unconditional Protein Design | UniRef50 | Perplexity (PPL)804.5 | 13 | |
| Multi-objective conditional protein design | PDFBench lysozyme-like superfamily conditional setting | PPL1.26e+3 | 4 | |
| Protein fitness steering | SPG1 STRSG Olson 2014 | Max Score0.7 | 4 | |
| Protein fitness steering | GRB2 HUMAN Faure 2021 | Max Score-0.2 | 4 | |
| Protein fitness steering | HIS7_YEAST Pokusaeva 2019 | Max Score0.77 | 4 | |
| Protein fitness steering | GFP_AEQVI_Sarkisyan 2016 | Max Score3.16 | 4 | |
| Protein fitness steering | CAPSD AAV2S Sinai 2021 | Max Score0.45 | 4 | |
| Protein fitness steering | RASK HUMAN Weng abundance 2022 | Max Score-0.28 | 4 | |
| Protein fitness steering | A4_HUMAN Seuma 2022 | Max Score-1.87 | 4 |