Sfcnn: a novel scoring function based on 3D convolutional neural network for accurate and stable protein–ligand affinity prediction

BACKGROUND: Computer-aided drug design provides an effective method of identifying lead compounds. However, success rates are significantly bottlenecked by the lack of accurate and reliable scoring functions needed to evaluate binding affinities of protein–ligand complexes. Therefore, many scoring functions based on machine learning or deep learning have been developed to improve prediction accuracies in recent years. In this work, we proposed a novel featurization method, generating a new scoring function model based on 3D convolutional neural network. RESULTS: This work showed the results from testing four architectures and three featurization methods, and outlined the development of a novel deep 3D convolutional neural network scoring function model. This model simplified feature engineering, and in combination with Grad-CAM made the intermediate layers of the neural network more interpretable. This model was evaluated and compared with other scoring functions on multiple independent datasets. The Pearson correlation coefficients between the predicted binding affinities by our model and the experimental data achieved 0.7928, 0.7946, 0.6758, and 0.6474 on CASF-2016 dataset, CASF-2013 dataset, CSAR_HiQ_NRC_set, and Astex_diverse_set, respectively. Overall, our model performed accurately and stably enough in the scoring power to predict the binding affinity of a protein–ligand complex. CONCLUSIONS: These results indicate our model is an excellent scoring function, and performs well in scoring power for accurately and stably predicting the protein–ligand affinity. Our model will contribute towards improving the success rate of virtual screening, thus will accelerate the development of potential drugs or novel biologically active lead compounds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04762-3.