论文笔记Predicting Drug−Target Interaction Using a Novel Graph NeuralNetwork with 3D Structure-Embedded

1.标题

文献标题:Predicting Drug−Target Interaction Using a Novel Graph Neural Network with 3D Structure-Embedded Graph Representation

(标题居然放不下)

文章主要内容是用图神经网络(Graph Neural Network)预测药靶相互作用(Drug−Target Interaction) 

文章原文链接:https://doi.org/10.1021/acs.jcim.9b00387

摘要:We propose a novel deep learning approach for predicting drug−target interaction using a graph neural network. We introduce a distance-aware graph attention algorithm to differentiate various types of intermolecular interactions. Furthermore, we extract the graph feature of intermolecular interactions directly from the 3D structural information on the protein−ligand binding pose. Thus, the model can learn key features for accurate predictions of drug−target interaction rather than just memorize certain patterns of ligand molecules. As a result, our model shows better performance than docking and other deep learning methods for both virtual screening (AUROC of 0.968 for the DUD-E test set) and pose prediction (AUROC of 0.935 for the PDBbind test set). In addition, it can reproduce the natural population distribution of active molecules and inactive molecules.

翻译:我们提出了一种新颖的深度学习方法,用于使用图神经网络预测药物 - 靶标相互作用。我们引入了一种距离感知图注意算法来区分各种类型的分子间相互作用。此外,我们直接从蛋白质 - 配体结合姿势的3D结构信息中提取分子间相互作用的图形特征。因此,该模型可以学习关键特征,以准确预测药物 - 靶标相互作用,而不仅仅是记住配体分子的某些模式。因此,我们的模型在虚拟筛选(virtual screening)(DUD-E测试集的AUROC为0.968)和姿态预测(pose prediction)(PDBbind测试集的AUROC为0.935)方面表现出比分子对接和其他深度学习方法更好的性能。此外,它还可以再现活性分子和非活性分子的自然种群分布。

虚拟筛选(virtual screening)和姿态预测(pose prediction),后面这个名词是否翻译有误?姿态预测是什么?

pose指分子构象,应该是小分子(结合)构想预测,pose prediction 指小分子和蛋白质结合构想预测。 

再现活性分子和非活性分子的自然种群分布:指可以重现活性分子和非活性分子的(活性)空间分部特征。

空间分布特征:对于一个靶分子,全体小分子的活性在结构空间的分布,比如哪个(分子)结构空间是高活性,哪个结构空间是低活性,比如在一个三维的结构空间中,左上角是高活性,右下角是低活性。结构决定活性。

2.Method

2.1 Embedding the Structural Information on a Protein− Ligand Complex.

模型的输入是 蛋白质-配体复合物 。文章用两个邻接矩阵(A1,A2)表示蛋白质和配体之间的结构信息。A1表示纯共价相互作用,A2表示共价相互作用和非共价分子间相互作用。 下图中,红色连接的就是共价相互作用,蓝色是非共价分子间相互作用,圆都是原子。蛋白质取的是配体8A范围内的原子。A1 A2取值如下:

 

2.2 Distance-Aware Graph Attention Mechanism and Gate Augmentation Algorithm

The inputs of our graph attention layer are adjacency matrix, A, and the set of node features, x

3.数据

对接后 取配体原子最小距离小于 8A 的蛋白质原子,使用 氢原子 补充 饱和化学价, 蛋白质 - 配体复合物的图 只考虑重原子。

 

Semi-supervised classification with graph convolutional networks (GCNs) is a method for predicting labels for nodes in a graph. GCNs are a type of neural network that operates on graph-structured data, where each node in the graph represents an entity (such as a person, a product, or a webpage) and edges represent relationships between entities. The semi-supervised classification problem arises when we have a graph where only a small subset of nodes have labels, and we want to predict the labels of the remaining nodes. GCNs can be used to solve this problem by learning to propagate information through the graph, using the labeled nodes as anchors. The key idea behind GCNs is to use a graph convolution operation to aggregate information from a node's neighbors, and then use this aggregated information to update the node's representation. This operation is then repeated over multiple layers, allowing the network to capture increasingly complex relationships between nodes. To train a GCN for semi-supervised classification, we use a combination of labeled and unlabeled nodes as input, and optimize a loss function that encourages the network to correctly predict the labels of the labeled nodes while also encouraging the network to produce smooth predictions across the graph. Overall, semi-supervised classification with GCNs is a powerful and flexible method for predicting labels on graph-structured data, and has been successfully applied to a wide range of applications including social network analysis, drug discovery, and recommendation systems.
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