LVPocket: integrated 3D global-local information to protein binding pockets prediction with transfer learning of protein structure classification

• Published in: Journal of cheminformatics Vol. 16; no. 1; pp. 79 - 12
• Main Authors: Zhou, Ruifeng, Fan, Jing, Li, Sishu, Zeng, Wenjie, Chen, Yilun, Zheng, Xiaoshan, Chen, Hongyang, Liao, Jun
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 07.07.2024; BioMed Central Ltd; Springer Nature B.V; BMC
• Subjects: Binding; Chemistry; Chemistry and Materials Science; Computational Biology/Bioinformatics; Computer Applications in Chemistry; Convolution; Datasets; Deep learning; Documentation and Information in Chemistry; Folding; Folding structures; Functionals; Prediction models; Protein binding; Protein binding pockets prediction; Protein folding; Protein structural classification; Protein structure; Proteins; Structure-function relationships; Theoretical and Computational Chemistry; Transfer learning; Transformer encoder; Protein binding pockets prediction; Transformer encoder; Protein structural classification; Transfer learning
• ISSN: 1758-2946; 1758-2946
• DOI: 10.1186/s13321-024-00871-8

Background Previous deep learning methods for predicting protein binding pockets mainly employed 3D convolution, yet an abundance of convolution operations may lead the model to excessively prioritize local information, thus overlooking global information. Moreover, it is essential for us to account for the influence of diverse protein folding structural classes. Because proteins classified differently structurally exhibit varying biological functions, whereas those within the same structural class share similar functional attributes. Results We proposed LVPocket, a novel method that synergistically captures both local and global information of protein structure through the integration of Transformer encoders, which help the model achieve better performance in binding pockets prediction. And then we tailored prediction models for data of four distinct structural classes of proteins using the transfer learning. The four fine-tuned models were trained on the baseline LVPocket model which was trained on the sc-PDB dataset. LVPocket exhibits superior performance on three independent datasets compared to current state-of-the-art methods. Additionally, the fine-tuned model outperforms the baseline model in terms of performance. Scientific contribution We present a novel model structure for predicting protein binding pockets that provides a solution for relying on extensive convolutional computation while neglecting global information about protein structures. Furthermore, we tackle the impact of different protein folding structures on binding pocket prediction tasks through the application of transfer learning methods. Graphical Abstract