Contrastive pre-training and 3D convolution neural network for RNA and small molecule binding affinity prediction
Saisai Sun, Lin Gao- Computational Mathematics
- Computational Theory and Mathematics
- Computer Science Applications
- Molecular Biology
- Biochemistry
- Statistics and Probability
Abstract
Motivation
The diverse structures and functions inherent in RNAs present a wealth of potential drug targets. Some small molecules are anticipated to serve as leading compounds, providing guidance for the development of novel RNA-targeted therapeutics. Consequently, the determination of RNA-small molecule binding affinity is a critical undertaking in the landscape of RNA-targeted drug discovery and development. Nevertheless, to date, no computational method for RNA-small molecule binding affinity prediction has been proposed. The prediction of RNA-small molecule binding affinity remains a significant challenge. The development of a computational model is deemed essential to effectively extract relevant features and predict RNA-small molecule binding affinity accurately.
Results
In this study, we introduced RLaffinity, a novel deep learning model designed for the prediction of RNA-small molecule binding affinity based on 3D structures. RLaffinity integrated information from RNA pockets and small molecules, utilizing a 3D convolutional neural network (3D-CNN) coupled with a contrastive learning-based self-supervised pre-training model. To the best of our knowledge, RLaffinity was the first computational method for the prediction of RNA-small molecule binding affinity. Our experimental results exhibited RLaffinity's superior performance compared to baseline methods, revealing by all metrics. The efficacy of RLaffinity underscores the capability of 3D-CNN to accurately extract both global pocket information and local neighbor nucleotide information within RNAs. Notably, the integration of a self-supervised pre-training model significantly enhanced predictive performance. Ultimately, RLaffinity was also proved as a potential tool for RNA-targeted drugs virtual screening.
Availability
https://github.com/SaisaiSun/RLaffinity
Supplementary information
Supplementary data are available at Bioinformatics online.