ProteinRPN: Towards Accurate Protein Function Prediction with Graph-Based Region Proposals

TL;DR

ProteinRPN introduces a graph-based region proposal approach inspired by computer vision to improve the accuracy of protein function prediction by identifying key functional regions within protein structures.

Contribution

The paper presents a novel region proposal network for proteins that enhances functional residue localization and improves GO term prediction accuracy.

Findings

Significant improvement in GO term prediction accuracy.

Effective localization of functional residues within protein structures.

Enhanced performance over existing structure-based models.

Abstract

Protein function prediction is a crucial task in bioinformatics, with significant implications for understanding biological processes and disease mechanisms. While the relationship between sequence and function has been extensively explored, translating protein structure to function continues to present substantial challenges. Various models, particularly, CNN and graph-based deep learning approaches that integrate structural and functional data, have been proposed to address these challenges. However, these methods often fall short in elucidating the functional significance of key residues essential for protein functionality, as they predominantly adopt a retrospective perspective, leading to suboptimal performance. Inspired by region proposal networks in computer vision, we introduce the Protein Region Proposal Network (ProteinRPN) for accurate protein function prediction. Specifically, the region proposal module component of ProteinRPN identifies potential functional regions (anchors) which are refined through the hierarchy-aware node drop pooling layer favoring nodes with defined secondary structures and spatial proximity. The representations of the predicted functional nodes are enriched using attention mechanisms and subsequently fed into a Graph Multiset Transformer, which is trained with supervised contrastive (SupCon) and InfoNCE losses on perturbed protein structures. Our model demonstrates significant improvements in predicting Gene Ontology (GO) terms, effectively localizing functional residues within protein structures. The proposed framework provides a robust, scalable solution for protein function annotation, advancing the understanding of protein structure-function relationships in computational biology.