DynamicDTA: Drug-Target Binding Affinity Prediction Using Dynamic Descriptors and Graph Representation.

motivationPredicting drug-target binding affinity (DTA) is essential for identifying potential therapeutic candidates in drug discovery. However, most existing models rely heavily on static protein structures, often overlooking the dynamic nature of proteins, which is crucial for capturing conformational flexibility that will be beneficial for protein binding interactions.

methodsWe introduce DynamicDTA, an innovative deep learning framework that incorporates static and dynamic protein features to enhance DTA prediction. The proposed DynamicDTA takes three types of inputs, including drug sequence, protein sequence, and dynamic descriptors. A molecular graph representation of the drug sequence is generated and subsequently processed through graph convolutional network, while the protein sequence is encoded using dilated convolutions. Dynamic descriptors, such as root mean square fluctuation, are processed through a multi-layer perceptron. These embedding features are fused with static protein features using cross-attention, and a tensor fusion network integrates all three modalities for DTA prediction.

resultsExtensive experiments on three datasets demonstrate that DynamicDTA achieves by at least 3.4% improvement in AVAILABILITY AND IMPLEMENTATION: The source code is publicly available and can be accessed at https://github.com/shmily-ld/DynamicDTA .