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PLI Analyzer for Data-driven Validation of AI Predicted Biomolecular Interfaces

Liang, F.; Srinivasan, S.; Chang, H. Y.

2025-10-01 bioinformatics
10.1101/2025.09.29.678845 bioRxiv
Show abstract

PLI-Analyzer is a computational tool for detailed analysis of protein, RNA, and DNA interaction interfaces, combining atomic-level contact detection with domain annotations from UniProt and InterPro. It offers customizable interaction thresholds, residue-level output, and compatibility with AI-generated structures, enabling precise validation and interpretation of contact dynamics. We applied PLI-Analyzer to evaluate high-quality protein-protein complexes predicted by AlphaFold-3 and Boltz-2, revealing notable differences in predicted interfaces and confidence scores. These findings highlight current limitations in generative structure models specifically for macromolecular complexes and underscore the need for robust, domain-informed evaluation frameworks in structural bioinformatics.

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