Title: VenusX: Unlocking Fine-Grained Functional Understanding of Proteins
Primary area: datasets and benchmarks
Keywords: protein substructure prediction, protein function prediction, molecule representation learning, pre-trained protein language model, fine-grained protein annotation

Abstract: Deep learning models have driven significant progress in predicting protein function and interactions at the protein level. While these advancements have been invaluable for many biological applications such as enzyme engineering and function annotation, a more detailed perspective is essential for understanding protein functional mechanisms and evaluating the biological knowledge captured by models. This study introduces VenusX, the first benchmark designed to assess protein representation learning with a focus on fine-grained intra-protein functional understanding. VenusX comprises three major task categories across six types of annotations, including residue-level binary classification, fragment-level multi-class classification, and pairwise functional similarity scoring for identifying critical active sites, binding sites, conserved sites, motifs, domains, and epitopes. The benchmark features over 878,000 samples curated from major open-source databases such as InterPro, BioLiP, and SAbDab. By providing mixed-family and cross-family splits at three sequence identity thresholds, our benchmark enables a comprehensive assessment of model performance on both in-distribution and out-of-distribution scenarios. For baseline evaluation, we assess a diverse set of popular and open-source models, including pre-trained protein language models, sequence-structure hybrids, structure-based methods, and alignment-based techniques. Their performance is reported across all benchmark datasets and evaluation settings using multiple metrics, offering a thorough comparison and a strong foundation for future research. Our code (https://anonymous.4open.science/r/VenusX-4674), data (https://huggingface.co/collections/anonymous-researcher-123/venusx-68cc5163ade527b0974bab29), and a leaderboard (https://anonymous-researcher-816.github.io/) are provided as open-source resources.

TL;DR: We present VenusX, the first large-scale benchmark for fine-grained protein understanding, featuring over 878k annotations across 17 tasks for residues, fragments, and domains.