mlsanityData to 14 Oct 2026

Steering Protein Language Models

arXiv 2509.07983 ↗First posted 1 Jul 2025q-bio.BM cs.LGcited by 7

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Abstract (arXiv)

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.

Key facts. Cited by 7 papers in the map (data through 14 Oct 2026). Builds on 21 of its 46 references that are in the map. First posted on arXiv 1 Jul 2025.

Builds on

21 of 46 references.

References · 21

  1. 2023Representation Engineering: A Top-Down Approach to AI Transparencycited by 1,336
  2. 2023Inference-Time Intervention: Eliciting Truthful Answers from a Language Modelcited by 1,302
  3. 2023Steering Llama 2 via Contrastive Activation Additioncited by 1,085
  4. 2023In-context Vectors: Making In Context Learning More Effective and Controllable Through Latent Space Steeringcited by 245
  5. 2022Extracting Latent Steering Vectors from Pretrained Language Modelscited by 225
  6. 2024Programming Refusal with Conditional Activation Steeringcited by 206
  7. 2022ProGen2: Exploring the Boundaries of Protein Language Modelscited by 159
  8. 2020ProGen: Language Modeling for Protein Generationcited by 128
  9. 2024Personalized Steering of Large Language Models: Versatile Steering Vectors Through Bi-directional Preference Optimizationcited by 118
  10. 2022Accelerating Bayesian Optimization for Biological Sequence Design with Denoising Autoencoderscited by 102
  11. 2022Tranception: protein fitness prediction with autoregressive transformers and inference-time retrievalcited by 79
  12. 2023Structure-informed Language Models Are Protein Designerscited by 68
9 more
  1. 2020AdaLead: A simple and robust adaptive greedy search algorithm for sequence designcited by 65
  2. 2024Spectral Editing of Activations for Large Language Model Alignmentcited by 56
  3. 2024BioT5+: Towards Generalized Biological Understanding with IUPAC Integration and Multi-task Tuningcited by 54
  4. 2024ProLLaMA: A Protein Large Language Model for Multi-Task Protein Language Processingcited by 53
  5. 2023Improving Protein Optimization with Smoothed Fitness Landscapescited by 21
  6. 2021Deep Generative Modeling for Protein Designcited by 17
  7. 2024Discovering Bias in Latent Space: An Unsupervised Debiasing Approachcited by 15
  8. 2024Robust Optimization in Protein Fitness Landscapes Using Reinforcement Learning in Latent Spacecited by 13
  9. 2024Multi-Scale Representation Learning for Protein Fitness Predictioncited by 11

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Cited by year (2026 to 14 Oct)

Citing papers per year: 2026: 7.

7 papers.

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  1. 2025Self Distillation Fine-Tuning of Protein Language Models Improves Versatility in Protein Design
  2. 2025Steering Generative Models with Experimental Data for Protein Fitness Optimization
  3. 2024Reinforcement Learning for Sequence Design Leveraging Protein Language Models
  4. 2025ProteinGuide: On-the-fly property guidance for protein sequence generative models
  5. 2024Diffusion Language Models Are Versatile Protein Learners
  6. 2026PFArena: Benchmarking Language Models for Protein Modification
  7. 2026Protein Language Models Diverge from Natural Language: Comparative Analysis and Improved Inference
  8. 2024TourSynbio: A Multi-Modal Large Model and Agent Framework to Bridge Text and Protein Sequences for Protein Engineering