General Protein Pretraining or Domain-Specific Designs? Benchmarking Protein Modeling on Realistic Applications

TL;DR

This paper introduces Protap, a benchmark for evaluating protein modeling methods across diverse real-world applications, highlighting the effectiveness of structural information and domain-specific priors over large-scale pretraining.

Contribution

Protap systematically compares various architectures and strategies on multiple realistic protein tasks, including novel industrially relevant applications.

Findings

Large-scale pretraining often underperforms supervised models on small datasets.

Structural information during fine-tuning can rival large pretraining models.

Domain-specific priors improve performance on specialized tasks.

Abstract

Recently, extensive deep learning architectures and pretraining strategies have been explored to support downstream protein applications. Additionally, domain-specific models incorporating biological knowledge have been developed to enhance performance in specialized tasks. In this work, we introduce $\textbf{Protap}$, a comprehensive benchmark that systematically compares backbone architectures, pretraining strategies, and domain-specific models across diverse and realistic downstream protein applications. Specifically, Protap covers five applications: three general tasks and two novel specialized tasks, i.e., enzyme-catalyzed protein cleavage site prediction and targeted protein degradation, which are industrially relevant yet missing from existing benchmarks. For each application, Protap compares various domain-specific models and general architectures under multiple pretraining settings. Our empirical studies imply that: (i) Though large-scale pretraining encoders achieve great results, they often underperform supervised encoders trained on small downstream training sets. (ii) Incorporating structural information during downstream fine-tuning can match or even outperform protein language models pretrained on large-scale sequence corpora. (iii) Domain-specific biological priors can enhance performance on specialized downstream tasks. Code and datasets are publicly available at https://github.com/Trust-App-AI-Lab/protap.