Motivation: Drug-target binding affinity (DTA) reflects the strength of the drug-target interaction; therefore, predicting the DTA can considerably benefit drug discovery by narrowing the search space and pruning drug-target (DT) pairs with low binding affinity scores. Representation learning using deep neural networks has achieved promising performance compared with traditional machine learning methods; hence, extensive research efforts have been made in learning the feature representation of proteins and compounds. However, such feature representation learning relies on a large-scale labelled dataset, which is not always available. Results: We present an end-to-end deep learning framework, ELECTRA-DTA, to predict the binding affinity of drug-target pairs. This framework incorporates an unsupervised learning mechanism to train two ELECTRA-based contextual embedding models, one for protein amino acids and the other for compound SMILES string encoding. In addition, ELECTRA-DTA leverages a squeeze-and-excitation (SE) convolutional neural network block stacked over three fully connected layers to further capture the sequential and spatial features of the protein sequence and SMILES for the DTA regression task. Experimental evaluations show that ELECTRA-DTA outperforms various state-of-the-art DTA prediction models, especially with the challenging, interaction-sparse BindingDB dataset. In target selection and drug repurposing for COVID-19, ELECTRA-DTA also offers competitive performance, suggesting its potential in speeding drug discovery and generalizability for other compound- or protein-related computational tasks.

Motivation: Accurate prediction of drug–target binding affinity (DTA) is crucial for drug discovery. The increase in the publication of large-scale DTA datasets enables the development of various computational methods for DTA prediction. Numerous deep learning-based methods have been proposed to predict affinities, some of which only utilize original sequence information or complex structures, but the effective combination of various information and protein-binding pockets have not been fully mined. Therefore, a new method that integrates available key information is urgently needed to predict DTA and accelerate the drug discovery process. Results: In this study, we propose a novel deep learning-based predictor termed DataDTA to estimate the affinities of drug–target pairs. DataDTA utilizes descriptors of predicted pockets and sequences of proteins, as well as low-dimensional molecular features and SMILES strings of compounds as inputs. Specifically, the pockets were predicted from the three-dimensional structure of proteins and their descriptors were extracted as the partial input features for DTA prediction. The molecular representation of compounds based on algebraic graph features was collected to supplement the input information of targets. Furthermore, to ensure effective learning of multiscale interaction features, a dual-interaction aggregation neural network strategy was developed. DataDTA was compared with state-of-the-art methods on different datasets, and the results showed that DataDTA is a reliable prediction tool for affinities estimation. Specifically, the concordance index (CI) of DataDTA is 0.806 and the Pearson correlation coefficient (R) value is 0.814 on the test dataset, which is higher than other methods. Availability and implementation: The codes and datasets of DataDTA are available at https://github.com/YanZhu06/DataDTA.

Accurately predicting the Remaining Useful Life (RUL) of lithium-ion batteries is crucial for battery management systems. Deep learning-based methods have been shown to be effective in predicting RUL by leveraging battery capacity time series data. However, the representation learning of features such as long-distance sequence dependencies and mutations in capacity time series still needs to be improved. To address this challenge, this paper proposes a novel deep learning model, the MLP-Mixer and Mixture of Expert (MMMe) model, for RUL prediction. The MMMe model leverages the Gated Recurrent Unit and Multi-Head Attention mechanism to encode the sequential data of battery capacity to capture the temporal features and a re-zero MLP-Mixer model to capture the high-level features. Additionally, we devise an ensemble predictor based on a Mixture-of-Experts (MoE) architecture to generate reliable RUL predictions. The experimental results on public datasets demonstrate that our proposed model significantly outperforms other existing methods, providing more reliable and precise RUL predictions while also accurately tracking the capacity degradation process. Our code and dataset are available at the website of github.

The capability to predict the potential drug binding affinity against a protein target has always been a fundamental challenge in silico drug discovery. The traditional experiments in vitro and in vivo are costly and time-consuming which need to search over large compound space. Recent years have witnessed significant success on deep learning-based models for drug-target binding affinity prediction task. Following the recent success of the Transformer model, we propose a multigranularity protein–ligand interaction (MGPLI) model, which adopts the Transformer encoders to represent the character-level features and fragment-level features, modeling the possible interaction between residues and atoms or their segments. In addition, we use the convolutional neural network to extract higher-level features based on transformer encoder outputs and a highway layer to fuse the protein and drug features. We evaluate MGPLI on different protein–ligand interaction datasets and show the improvement of prediction performance compared to state-of-the-art baselines. The model scripts are available at https://github.com/IILab-Resource/MGDTA.git

Accurate prediction of small molecule modulators targeting protein-protein interactions (PPIMs) remains a significant challenge in drug discovery. Existing machine learning-based models rely on manual feature engineering, which is tedious and task-specific. Recently, deep learning models based on graph neural networks have made remarkable progress in molecular representation learning. However, many graph-based approaches ignore molecular hierarchical structure modeling guided by domain knowledge. In chemistry, the functional groups of a molecule determine its interaction with specific targets. Therefore, we propose a hierarchical graph neural network framework (called HiGPPIM) for predicting PPIMs by integrating atom-level and functional group-level features of molecules. HiGPPIM constructs atom-level and functional group-level graphs based on chemical knowledge and learns graph representations using graph attention networks. Furthermore, a hypergraph attention network is designed in HiGPPIM to aggregate and transform two-level graph information. We evaluate the performance of HiGPPIM on eight PPI families and two prediction tasks, namely PPIM identification and potency prediction. Experimental results demonstrate that HiGPPIM achieves state-of-the-art performance on both tasks and that using functional group information to guide PPIM prediction is effective. The source code and datasets are freely available at https://github.com/1zzt/HiGPPIM.