An Integrated Deep-Learning Framework for Peptide-Protein Interaction Prediction and Target-Conditioned Peptide Generation with ConGA-PepPI and TC-PepGen

Fuente: arXiv
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Main Authors: Tang, Chupei, Kong, Junxiao, Tang, Moyu, Wang, Di, Zhai, Jixiu, Xie, Ronghao, Sima, Shangkun, Lu, Tianchi
Format: Preprint
Published: 2026
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author Tang, Chupei
Kong, Junxiao
Tang, Moyu
Wang, Di
Zhai, Jixiu
Xie, Ronghao
Sima, Shangkun
Lu, Tianchi
author_facet Tang, Chupei
Kong, Junxiao
Tang, Moyu
Wang, Di
Zhai, Jixiu
Xie, Ronghao
Sima, Shangkun
Lu, Tianchi
contents Motivation: Peptide-protein interactions (PepPIs) are central to cellular regulation and peptide therapeutics, but experimental characterization remains too slow for large-scale screening. Existing methods usually emphasize either interaction prediction or peptide generation, leaving candidate prioritization, residue-level interpretation, and target-conditioned expansion insufficiently integrated. Results: We present an integrated framework for early-stage peptide screening that combines a partner-aware prediction and localization model (ConGA-PepPI) with a target-conditioned generative model (TC-PepGen). ConGA-PepPI uses asymmetric encoding, bidirectional cross-attention, and progressive transfer from pair prediction to binding-site localization, while TC-PepGen preserves target information throughout autoregressive decoding via layerwise conditioning. In five-fold cross-validation, ConGA-PepPI achieved 0.839 accuracy and 0.921 AUROC, with binding-site AUPR values of 0.601 on the protein side and 0.950 on the peptide side, and remained competitive on external benchmarks. Under a controlled length-conditioned benchmark, 40.39% of TC-PepGen peptides exceeded native templates in AlphaFold 3 ipTM, and unconstrained generation retained evidence of target-conditioned signal.
format Preprint
id arxiv_https___arxiv_org_abs_2604_18467
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle An Integrated Deep-Learning Framework for Peptide-Protein Interaction Prediction and Target-Conditioned Peptide Generation with ConGA-PepPI and TC-PepGen
Tang, Chupei
Kong, Junxiao
Tang, Moyu
Wang, Di
Zhai, Jixiu
Xie, Ronghao
Sima, Shangkun
Lu, Tianchi
Machine Learning
Artificial Intelligence
Motivation: Peptide-protein interactions (PepPIs) are central to cellular regulation and peptide therapeutics, but experimental characterization remains too slow for large-scale screening. Existing methods usually emphasize either interaction prediction or peptide generation, leaving candidate prioritization, residue-level interpretation, and target-conditioned expansion insufficiently integrated. Results: We present an integrated framework for early-stage peptide screening that combines a partner-aware prediction and localization model (ConGA-PepPI) with a target-conditioned generative model (TC-PepGen). ConGA-PepPI uses asymmetric encoding, bidirectional cross-attention, and progressive transfer from pair prediction to binding-site localization, while TC-PepGen preserves target information throughout autoregressive decoding via layerwise conditioning. In five-fold cross-validation, ConGA-PepPI achieved 0.839 accuracy and 0.921 AUROC, with binding-site AUPR values of 0.601 on the protein side and 0.950 on the peptide side, and remained competitive on external benchmarks. Under a controlled length-conditioned benchmark, 40.39% of TC-PepGen peptides exceeded native templates in AlphaFold 3 ipTM, and unconstrained generation retained evidence of target-conditioned signal.
title An Integrated Deep-Learning Framework for Peptide-Protein Interaction Prediction and Target-Conditioned Peptide Generation with ConGA-PepPI and TC-PepGen
topic Machine Learning
Artificial Intelligence
url https://arxiv.org/abs/2604.18467