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Motivation Fast and accurate classification of ligand-binding sites in proteins with respect to the class of binding molecules is invaluable not only to the automatic functional annotation of large datasets of protein structures but also to projects in protein evolution, protein engineering and drug development. Deep learning techniques, which have already been successfully applied to address challenging problems across various fields, are inherently suitable to classify ligand-binding pockets. Our goal is to demonstrate that off-the-shelf deep learning models can be employed with minimum development effort to recognize nucleotide- and heme-binding sites with a comparable accuracy to highly specialized, voxel-based methods. Results We developed BionoiNet, a new deep learning-based framework implementing a popular ResNet model for image classification. BionoiNet first transforms the molecular structures of ligand-binding sites to 2D Voronoi diagrams, which are then used as the input to a pretrained convolutional neural network classifier. The ResNet model generalizes well to unseen data achieving the accuracy of 85.6% for nucleotide- and 91.3% for heme-binding pockets. BionoiNet also computes significance scores of pocket atoms, called BionoiScores, to provide meaningful insights into their interactions with ligand molecules. BionoiNet is a lightweight alternative to computationally expensive 3D architectures. Availability and implementation BionoiNet is implemented in Python with the source code freely available at: https://github.com/CSBG-LSU/BionoiNet. Supplementary information Supplementary data are available at Bioinformatics online.

Genomic profiles of cancer cells provide valuable information on genetic alterations in cancer. Several recent studies employed these data to predict the response of cancer cell lines to treatment with drugs. Nonetheless, due to the multifactorial phenotypes and intricate mechanisms of cancer, the accurate prediction of the effect of pharmacotherapy on a specific cell line based on the genetic information alone is problematic. High prediction accuracies reported in the literature likely result from significant overlaps among training, validation, and testing sets, making many predictors inapplicable to new data. To address these issues, we developed GraphGR, a graph neural network with sophisticated attention propagation mechanisms to predict the therapeutic effects of kinase inhibitors across various tumors. Emphasizing on the system-level complexity of cancer, GraphGR integrates multiple heterogeneous data, such as biological networks, genomics, inhibitor profiling, and genedisease associations, into a unified graph structure. In order to construct diverse and information-rich cancer-specific networks, we devised a novel graph reduction protocol based on not only the topological information, but also the biological knowledge. The performance of GraphGR, properly cross-validated at the tissue level, is 0.83 in terms of the area under the receiver operating characteristics, which is notably higher than those measured for other approaches on the same data. Finally, several new predictions are validated against the biomedical literature demonstrating that GraphGR generalizes well to unseen data, i.e. it can predict therapeutic effects across a variety of cancer cell lines and inhibitors. GraphGR is freely available to the academic community at https://github.com/pulimeng/GraphGR.