Li Yuguang, Tian Zhen, Nan Xiaofei, Zhang Shoutao, Zhou Qinglei, Lu Shuai
School of Computer and Artificial Intelligence, Zhengzhou University, Zhengzhou 450001, Henan, China.
Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou 324003, Zhejiang, China.
Brief Bioinform. 2025 Mar 4;26(2). doi: 10.1093/bib/bbaf079.
Protein-protein interactions play a fundamental role in biological systems. Accurate detection of protein-protein interaction sites (PPIs) remains a challenge. And, the methods of PPIs prediction based on biological experiments are expensive. Recently, a lot of computation-based methods have been developed and made great progress. However, current computational methods only focus on one form of protein, using only protein spatial conformation or primary sequence. And, the protein's natural hierarchical structure is ignored.
In this study, we propose a novel network architecture, HSSPPI, through hierarchical and spatial-sequential modeling of protein for PPIs prediction. In this network, we represent protein as a hierarchical graph, in which a node in the protein is a residue (residue-level graph) and a node in the residue is an atom (atom-level graph). Moreover, we design a spatial-sequential block for capturing complex interaction relationships from spatial and sequential forms of protein. We evaluate HSSPPI on public benchmark datasets and the predicting results outperform the comparative models. This indicates the effectiveness of hierarchical protein modeling and also illustrates that HSSPPI has a strong feature extraction ability by considering spatial and sequential information simultaneously.
The code of HSSPPI is available at https://github.com/biolushuai/Hierarchical-Spatial-Sequential-Modeling-of-Protein.
蛋白质-蛋白质相互作用在生物系统中起着基础性作用。准确检测蛋白质-蛋白质相互作用位点(PPI)仍然是一项挑战。而且,基于生物学实验的PPI预测方法成本高昂。最近,已经开发了许多基于计算的方法并取得了很大进展。然而,当前的计算方法仅关注一种蛋白质形式,仅使用蛋白质的空间构象或一级序列。并且,蛋白质的天然层次结构被忽略了。
在本研究中,我们提出了一种新颖的网络架构HSSPPI,通过对蛋白质进行层次化和空间-序列建模来进行PPI预测。在这个网络中,我们将蛋白质表示为一个层次图,其中蛋白质中的一个节点是一个残基(残基级图),残基中的一个节点是一个原子(原子级图)。此外,我们设计了一个空间-序列模块,用于从蛋白质的空间和序列形式中捕捉复杂的相互作用关系。我们在公共基准数据集上评估了HSSPPI,预测结果优于对比模型。这表明了蛋白质层次化建模的有效性,也说明了HSSPPI通过同时考虑空间和序列信息具有很强的特征提取能力。
HSSPPI的代码可在https://github.com/biolushuai/Hierarchical-Spatial-Sequential-Modeling-of-Protein获取。