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

TL;DR

DynamicDTA is a novel deep learning framework that integrates static and dynamic protein features with drug information to improve drug-target binding affinity predictions, addressing the limitations of static-only models.

Contribution

It introduces a multi-modal approach combining dynamic descriptors, graph representations, and cross-attention for enhanced DTA prediction, outperforming existing methods.

Findings

Achieves at least 3.4% improvement in RMSE over baseline models

Effectively incorporates dynamic protein features into DTA prediction

Demonstrates biological relevance through drug prediction and docking visualization

Abstract

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.