Topological deep learning for enhancing peptide-protein complex prediction.

ABSTRACT: Peptide-protein interactions are essential to biological processes and drug discovery, but selecting high-quality models from predicted complexes remains challenging due to high false positive rates (FPR). Here we introduce TopoDockQ, a topological deep learning model leveraging persistent combinatorial Laplacian (PCL) features to predict DockQ scores (p-DockQ) for accurately evaluating peptide-protein interface quality, aimed at enhancing precision and mitigating FPR in model selection. Compared to AlphaFold2's built-in confidence score, TopoDockQ reduces false positives by at least 42% and increases precision by 6.7% across five evaluation datasets filtered to ≤70% peptide-protein sequence identity, while maintaining relatively high recall and F1 scores. To support flexible peptide desig

SUBMITTER: Dai X 

PROVIDER: S-EPMC12612092 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature