BioScore: A Foundational Scoring Function For Diverse Biomolecular Complexes

TL;DR

BioScore is a versatile, geometry-based scoring framework that improves the assessment of diverse biomolecular complexes, outperforming traditional methods and enabling accurate predictions across various molecular systems.

Contribution

It introduces a dual-scale geometric graph learning framework that enhances generalizability and task performance in biomolecular structure assessment.

Findings

Outperforms or matches 70 existing methods across 16 benchmarks.

Pretraining boosts affinity prediction accuracy significantly.

Enables zero- and few-shot predictions with high correlation gains.

Abstract

Structural assessment of biomolecular complexes is vital for translating molecular models into functional insights, shaping our understanding of biology and aiding drug discovery. However, current structure-based scoring functions often lack generalizability across diverse biomolecular systems. We present BioScore, a foundational scoring function that addresses key challenges -- data sparsity, cross-system representation, and task compatibility -- through a dual-scale geometric graph learning framework with tailored modules for structure assessment and affinity prediction. BioScore supports a wide range of tasks, including affinity prediction, conformation ranking, and structure-based virtual screening. Evaluated on 16 benchmarks spanning proteins, nucleic acids, small molecules, and carbohydrates, BioScore consistently outperforms or matches 70 traditional and deep learning methods. Our newly proposed PPI Benchmark further enables comprehensive evaluation of protein-protein complex scoring. BioScore demonstrates broad applicability: (1) pretraining on mixed-structure data boosts protein-protein affinity prediction by up to 40% and antigen-antibody binding correlation by over 90%; (2) cross-system generalizability enables zero- and few-shot prediction with up to 71% correlation gain; and (3) its unified representation captures chemically challenging systems such as cyclic peptides, improving affinity prediction by over 60%. BioScore establishes a robust and generalizable framework for structural assessment across complex biomolecular landscapes.