Dataset Information

Structure-aware protein solubility prediction from sequence through graph convolutional network and predicted contact map.

ABSTRACT: Protein solubility is significant in producing new soluble proteins that can reduce the cost of biocatalysts or therapeutic agents. Therefore, a computational model is highly desired to accurately predict protein solubility from the amino acid sequence. Many methods have been developed, but they are mostly based on the one-dimensional embedding of amino acids that is limited to catch spatially structural information. In this study, we have developed a new structure-aware method GraphSol to predict protein solubility by attentive graph convolutional network (GCN), where the protein topology attribute graph was constructed through predicted contact maps only from the sequence. GraphSol was shown to substantially outperform other sequence-based methods. The model was proven to be stable by consistent [Formula: see text] of 0.48 in both the cross-validation and independent test of the eSOL dataset. To our best knowledge, this is the first study to utilize the GCN for sequence-based protein solubility predictions. More importantly, this architecture could be easily extended to other protein prediction tasks requiring a raw protein sequence.

SUBMITTER: Chen J

PROVIDER: S-EPMC7869490 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Structure-aware protein solubility prediction from sequence through graph convolutional network and predicted contact map.

Chen Jianwen J Zheng Shuangjia S Zhao Huiying H Yang Yuedong Y

Journal of cheminformatics 20210208 1

Protein solubility is significant in producing new soluble proteins that can reduce the cost of biocatalysts or therapeutic agents. Therefore, a computational model is highly desired to accurately predict protein solubility from the amino acid sequence. Many methods have been developed, but they are mostly based on the one-dimensional embedding of amino acids that is limited to catch spatially structural information. In this study, we have developed a new structure-aware method GraphSol to predi ...[more]

PMID: 33557952

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Project description:Site-specific proteolysis by the enzymatic cleavage of small linear sequence motifs is a key post-translational modification involved in physiology and disease. The ability to robustly and rapidly predict protease substrate specificity would also enable targeted proteolytic cleavage - editing - of a target protein by designed proteases. Current methods for predicting protease specificity are limited to sequence pattern recognition in experimentally-derived cleavage data obtained for libraries of potential substrates and generated separately for each protease variant. We reasoned that a more semantically rich and robust model of protease specificity could be developed by incorporating the three-dimensional structure and energetics of molecular interactions between protease and substrates into machine learning workflows. We present Protein Graph Convolutional Network (PGCN), which develops a physically-grounded, structure-based molecular interaction graph representation that describes molecular topology and interaction energetics to predict enzyme specificity. We show that PGCN accurately predicts the specificity landscapes of several variants of two model proteases: the NS3/4 protease from the Hepatitis C virus (HCV) and the Tobacco Etch Virus (TEV) proteases. Node and edge ablation tests identified key graph elements for specificity prediction, some of which are consistent with known biochemical constraints for protease:substrate recognition. We used a pre-trained PGCN model to guide the design of TEV protease libraries for cleaving two non-canonical substrates, and found good agreement with experimental cleavage results. Importantly, the model can accurately assess designs featuring diversity at positions not present in the training data. The described methodology should enable the structure-based prediction of specificity landscapes of a wide variety of proteases and the construction of tailor-made protease editors for site-selectively and irreversibly modifying chosen target proteins.

Dataset Information

Structure-aware protein solubility prediction from sequence through graph convolutional network and predicted contact map.

Publications

Structure-aware protein solubility prediction from sequence through graph convolutional network and predicted contact map.

Similar Datasets

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