Kavli Affiliate: Dan Luo
| First 5 Authors: Dan Luo, Jinyu Zhou, Le Xu, Sisi Yuan, Xuan Lin
| Summary:
Predicting 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. We 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. Extensive experiments on three datasets
demonstrate that DynamicDTA achieves by at least 3.4% improvement in RMSE score
with comparison to seven state-of-the-art baseline methods. Additionally,
predicting novel drugs for Human Immunodeficiency Virus Type 1 and visualizing
the docking complexes further demonstrates the reliability and biological
relevance of DynamicDTA.
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