Fine-tuning protein language models boosts predictions across diverse tasks

Prediction methods inputting embeddings from protein Language Models (pLMs) have reached or even surpassed state-of-the-art (SOTA) performance on many protein prediction tasks. In natural language processing (NLP) fine-tuning large Language Models (LLMs) has become the de facto standard. In contrast, most pLM-based protein predictions do not back-propagate to the pLM. Here, we compared the fine-tuning of three SOTA pLMs (ESM2, ProtT5, Ankh) on eight different tasks. Two results stood out. Firstly, task-specific supervised fine-tuning almost always improved downstream predictions. Secondly, parameter-efficient fine-tuning could reach similar improvements consuming substantially fewer resources at up to 4.5-fold acceleration of training over fine-tuning full models. Our results suggested to always try fine-tuning, in particular for problems with small datasets, such as for fitness landscape predictions of a single protein. For ease of adaptability, we provided easy-to-use notebooks to fine-tune all models used during this work for per-protein (pooling) and per-residue prediction tasks at https://github.com/RSchmirler/data-repo_plm-finetune-eval.