论文标题
GEFA:药物目标亲和力预测的早期融合方法
GEFA: Early Fusion Approach in Drug-Target Affinity Prediction
论文作者
论文摘要
预测化合物与靶标之间的相互作用对于快速的药物重新利用至关重要。深度学习已成功地应用于药物目标亲和力(DTA)问题。但是,以前的基于深度学习的方法忽略了建模药物与蛋白质残基之间直接相互作用的建模。这将导致对目标表示的学习不准确,这可能会因药物结合效应而改变。此外,以前的DTA方法仅基于DTA数据集中的少量蛋白质序列学习蛋白质表示,同时忽略了DTA数据集外的蛋白质的使用。我们提出了GEFA(图表早期融合亲和力),这是一种新型的图形神经网络,具有注意机制,以解决因结合效应而解决目标表示的变化。具体而言,将药物建模为原子图,然后在较大的残基 - 药物络合物图中用作节点。最终的模型是表达的深嵌套图神经网络。我们还使用预先训练的蛋白质表示,该蛋白质由最近学习上下文化蛋白表示的努力提供支持。实验是在不同的环境下进行的,以评估诸如新药物或靶标等情况。结果证明了预训练的蛋白质嵌入的有效性以及GEFA在对嵌套的靶标相互作用建模时的优势。
Predicting the interaction between a compound and a target is crucial for rapid drug repurposing. Deep learning has been successfully applied in drug-target affinity (DTA) problem. However, previous deep learning-based methods ignore modeling the direct interactions between drug and protein residues. This would lead to inaccurate learning of target representation which may change due to the drug binding effects. In addition, previous DTA methods learn protein representation solely based on a small number of protein sequences in DTA datasets while neglecting the use of proteins outside of the DTA datasets. We propose GEFA (Graph Early Fusion Affinity), a novel graph-in-graph neural network with attention mechanism to address the changes in target representation because of the binding effects. Specifically, a drug is modeled as a graph of atoms, which then serves as a node in a larger graph of residues-drug complex. The resulting model is an expressive deep nested graph neural network. We also use pre-trained protein representation powered by the recent effort of learning contextualized protein representation. The experiments are conducted under different settings to evaluate scenarios such as novel drugs or targets. The results demonstrate the effectiveness of the pre-trained protein embedding and the advantages our GEFA in modeling the nested graph for drug-target interaction.