论文标题

HAC-NET:一种基于混合注意力的卷积神经网络,用于高度准确的蛋白质 - 配体结合亲和力预测

HAC-Net: A Hybrid Attention-Based Convolutional Neural Network for Highly Accurate Protein-Ligand Binding Affinity Prediction

论文作者

Kyro, Gregory W., Brent, Rafael I., Batista, Victor S.

论文摘要

从图像检测和图理论中应用深度学习概念具有极大的先进蛋白质结合亲和力预测,这是对药物发现和蛋白质工程的巨大影响的挑战。我们通过设计一种新颖的深度学习体系结构来建立这些进步,该架构由频道关注的三维卷积神经网络组成,并利用基于注意力的节点特征的聚合来利用渠道关注和两个图形卷积网络。 HAC-NET(基于混合注意力的卷积神经网络)在PDBBIND v.2016 CORE SET上获得最新的结果,这是该领域最广泛认可的基准。我们使用多个火车测试拆分来广泛评估模型的普遍性,每种裂纹都可以最大化蛋白质结构,蛋白质序列或配体在训练和测试集中配合物的扩展连接指纹。此外,我们执行10倍的交叉验证,在训练和测试集中配体的微笑字符串之间的相似性截断,还评估了HAC-NET在低质量数据上的性能。我们设想,该模型可以扩展到与基于结构的生物分子财产预测相关的广泛监督学习问题。我们所有的软件均可在https://github.com/gregory-kyro/hac-net/上作为开源,并且可以通过PYPI获得Hacnet Python软件包。

Applying deep learning concepts from image detection and graph theory has greatly advanced protein-ligand binding affinity prediction, a challenge with enormous ramifications for both drug discovery and protein engineering. We build upon these advances by designing a novel deep learning architecture consisting of a 3-dimensional convolutional neural network utilizing channel-wise attention and two graph convolutional networks utilizing attention-based aggregation of node features. HAC-Net (Hybrid Attention-Based Convolutional Neural Network) obtains state-of-the-art results on the PDBbind v.2016 core set, the most widely recognized benchmark in the field. We extensively assess the generalizability of our model using multiple train-test splits, each of which maximizes differences between either protein structures, protein sequences, or ligand extended-connectivity fingerprints of complexes in the training and test sets. Furthermore, we perform 10-fold cross-validation with a similarity cutoff between SMILES strings of ligands in the training and test sets, and also evaluate the performance of HAC-Net on lower-quality data. We envision that this model can be extended to a broad range of supervised learning problems related to structure-based biomolecular property prediction. All of our software is available as open source at https://github.com/gregory-kyro/HAC-Net/, and the HACNet Python package is available through PyPI.

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