LipoPU: Pocket-level Prediction of Lipid-Protein Interactions via Positive-Unlabeled Learning

Abstract (source: OpenReview · © authors)

Computational identification of lipid-binding proteins is critical for both fundamental research and therapeutic development. Existing models are typically trained in a fully supervised manner, treating unlabeled samples as negatives. However, missing evidence does not imply non-binding, leading to systematic false negatives. Pocket-level lipid-binding prediction also remains underexplored compared to residue- or sequence-level approaches. To bridge these gaps, we present **LipoPU**, a pocket-centric predictor that formulates lipid-binding learning under a ranking-based positive-unlabeled objective, and supports both binary lipid-binding detection and multi-label lipid category prediction. LipoPU learns an attention-based pocket representation that is robust to ambiguous pocket definitions while providing residue-level interpretability. Experiments show consistent gains over supervised baselines and prior pocket-level work, and a structural case study recovers a literature-supported allosteric lipid-binding pocket while highlighting biologically informative residues.

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