Share your thoughts, 1 month free Claude Pro on usSee more
WorkDL logo mark

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.

Long-Kai Huang, Rongyi Zhu, Bing He, Jianhua Yao• 2025

Related benchmarks

TaskDatasetResultRank
Unconditional Protein DesignUniRef50
Perplexity (PPL)804.5
13
Multi-objective conditional protein designPDFBench lysozyme-like superfamily conditional setting
PPL1.26e+3
4
Protein fitness steeringSPG1 STRSG Olson 2014
Max Score0.7
4
Protein fitness steeringGRB2 HUMAN Faure 2021
Max Score-0.2
4
Protein fitness steeringHIS7_YEAST Pokusaeva 2019
Max Score0.77
4
Protein fitness steeringGFP_AEQVI_Sarkisyan 2016
Max Score3.16
4
Protein fitness steeringCAPSD AAV2S Sinai 2021
Max Score0.45
4
Protein fitness steeringRASK HUMAN Weng abundance 2022
Max Score-0.28
4
Protein fitness steeringA4_HUMAN Seuma 2022
Max Score-1.87
4
Showing 9 of 9 rows

Other info

Follow for update