Predicting G protein-coupled receptor (GPCR) -ligand binding affinity plays a crucial role in drug development. However, determining GPCR-ligand binding affinities is time-consuming and resource-intensive. Although many studies used data-driven methods to predict binding affinity, most of these methods required protein 3D structure, which was often unknown. Moreover, part of these studies only considered the sequence characteristics of the protein, ignoring the secondary structure of the protein. The number of known GPCR for affinity prediction is only a few thousand, which is insufficient for deep learning training. Therefore, this study aimed to propose a deep transfer learning method called TrGPCR, which used dynamic transfer learning to solve the problem of insufficient GPCR data. We used the Binding Database (BindingDB) as the source domain and the GLASS (GPCR-Ligand Association) database as the target domain. We also introduced protein secondary structures, called pockets, as features to predict binding affinities. Compared with DeepDTA, our model improved by 5.2% on RMSE (root mean square error) and 4.5% on MAE (mean squared error).

The accurate prediction of drug-target affinity (DTA) is a crucial step in drug discovery and design. Traditional experiments are very expensive and time-consuming. Recently, deep learning methods have achieved notable performance improvements in DTA prediction. However, one challenge for deep learning-based models is appropriate and accurate representations of drugs and targets, especially the lack of effective exploration of target representations. Another challenge is how to comprehensively capture the interaction information between different instances, which is also important for predicting DTA. In this study, we propose AttentionMGT-DTA, a multi-modal attention-based model for DTA prediction. AttentionMGT-DTA represents drugs and targets by a molecular graph and binding pocket graph, respectively. Two attention mechanisms are adopted to integrate and interact information between different protein modalities and drug-target pairs. The experimental results showed that our proposed model outperformed state-of-the-art baselines on two benchmark datasets. In addition, AttentionMGT-DTA also had high interpretability by modeling the interaction strength between drug atoms and protein residues. Our code is available at https://github.com/JK-Liu7/AttentionMGT-DTA.

DNA-binding proteins (DBPs) have a significant impact on many life activities, so identification of DBPs is a crucial issue. And it is greatly helpful to understand the mechanism of protein-DNA interactions. In traditional experimental methods, it is significant time-consuming and labor-consuming to identify DBPs. In recent years, many researchers have proposed lots of different DBP identification methods based on machine learning algorithm to overcome shortcomings mentioned above. However, most existing methods cannot get satisfactory results. In this paper, we focus on developing a new predictor of DBPs, called Multi-View Hypergraph Restricted Kernel Machines (MV-H-RKM). In this method, we extract five features from the three views of the proteins. To fuse these features, we couple them by means of the shared hidden vector. Besides, we employ the hypergraph regularization to enforce the structure consistency between original features and the hidden vector. Experimental results show that the accuracy of MV-H-RKM is 84.09% and 85.48% on PDB1075 and PDB186 data set respectively, and demonstrate that our proposed method performs better than other state-of-the-art approaches. The code is publicly available at https://github.com/ShixuanGG/MV-H-RKM.

G protein-coupled receptors (GPCRs) account for about 40% to 50% of drug targets. Many human diseases are related to G protein coupled receptors. Accurate prediction of GPCR interaction is not only essential to understand its structural role, but also helps design more effective drugs. At present, the prediction of GPCR interaction mainly uses machine learning methods. Machine learning methods generally require a large number of independent and identically distributed samples to achieve good results. However, the number of available GPCR samples that have been marked is scarce. Transfer learning has a strong advantage in dealing with such small sample problems. Therefore, this paper proposes a transfer learning method based on sample similarity, using XGBoost as a weak classifier and using the TrAdaBoost algorithm based on JS divergence for data weight initialization to transfer samples to construct a data set. After that, the deep neural network based on the attention mechanism is used for model training. The existing GPCR is used for prediction. In short-distance contact prediction, the accuracy of our method is 0.26 higher than similar methods.