Co-evolution-based Metal-binding Residue Prediction with Graph Neural Networks

In computational structural biology, predicting metal-binding sites and their corresponding metal types is challenging due to the complexity of protein structures and interactions. Conventional sequence- and structure-based prediction approaches cannot capture the complex evolutionary relationships driving these interactions to facilitate understanding, while recent co-evolution-based approaches do not fully consider the entire structure of the co-evolved residue network. In this paper, we introduce MBGNN (Metal-Binding Graph Neural Network) that utilizes the entire co-evolved residue network and effectively captures the complex dependencies within protein structures via graph neural networks to enhance the prediction of co-evolved metal-binding residues and their associated metal types. Experimental results on a public dataset show that MBGNN outperforms existing co-evolution-based metal-binding prediction methods, and it is also competitive against recent sequence-based methods, showing the potential of integrating co-evolutionary insights with advanced machine learning to deepen our understanding of protein-metal interactions. The MBGNN code is publicly available atthis https URL.

@article{rastegari2025_2502.16189,
  title={ Co-evolution-based Metal-binding Residue Prediction with Graph Neural Networks },
  author={ Sayedmohammadreza Rastegari and Sina Tabakhi and Xianyuan Liu and Wei Sang and Haiping Lu },
  journal={arXiv preprint arXiv:2502.16189},
  year={ 2025 }
}