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WAWABILITY July 11–12, 2025 Washington DC. Big ideas. Bold Progress. Global Impact. Powered by TDIforAccess.

C-P.16: ProInterVal-BioXtal: A Web Server to Distinguish Biological Interfaces from Crystal Contacts Using Graph Deep Learning

Authors

Koc University
Damla Ovek Baydar
NCMBM University of Oslo
Ozlem Keskin
Koc University
Attila Gursoy
Koc University
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Accurate discrimination between biologically relevant protein-protein interfaces (PPIs) and crystallographic contacts is essential for reliable interpretation of macromolecular assemblies and their cellular functions. While X-ray crystallography remains a primary method for determining protein complex structures, crystallographic interfaces may be formed as a byproduct of the crystal packing. Therefore, robust computational approaches for interface annotation are needed. This study introduces ProInterVal-BioXtal, a web server that predicts class scores for PPIs, differentiating between biologically relevant and crystallographic interfaces. The method leverages protein representation learning and graph-based deep learning to capture structural and physicochemical features. Interface graphs derived from input complexes are processed by our novel graph-based contrastive model to learn interface representations which are used by a graph neural network for classification. The model is trained and validated on the MANY benchmark dataset comprising 5739 dimers with a balanced distribution of biological and crystal interfaces and evaluated on the DC benchmark dataset with curated interfaces of similar interface areas. On the DC test set, ProInterVal-BioXtal achieves 88% accuracy, 88% precision, and 85% F1 score, outperforming state-of-the-art methods including DeepRank-GNN, PRODIGY-CRYSTAL, EPPIC 3, PISA, and QSAlign. On an independent benchmark, the method achieves 83% accuracy and 0.91 AUC, surpassing DeepRank-GNN (AUC = 0.85). Through a user-friendly web interface, ProInterVal-BioXtal enables rapid predictions from PDB files or IDs, returning probabilistic classification scores. Our tool addresses a fundamental challenge in structural biology by utilizing graph-based protein representation which can detect complex interactions and dependencies. ProInterVal-BioXtal server is freely available at https://3dpath.ku.edu.tr/prointerval-bioxtal/

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