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Exploring protein-protein interaction sites (PPIS) is of significance to elucidating the intrinsic mechanisms of diverse biological processes. On this basis, recent studies have applied deep learning-based technologies to overcome the high cost of wet experiments for PPIS determination. However, the existing methods still suffer from two limitations that remain to be solved. Firstly, the process of feature aggregation in most methods only took into account node features, but ignored the complex edge features of the target residue to its neighbor residues, resulting in insufficient local feature extraction. Secondly, such feature aggregation was limited to aggregating spatially adjacent residues, and could not capture the "remote" residues that played a critical role in determining PPIS, which can be summed up as the lack of global feature at the residue level. To break the above limitations, a local-global structural information aggregation framework, LGS-PPIS, was proposed in this study, including two modules of edge-aware graph convolutional network (EA-GCN) and self-attention integrated with initial residual and identity mapping (SA-RIM), which achieved the aggregation of local and global information for PPIS prediction. Evaluation results of LGS-PPIS showed that the proposed method outperformed state-of-the-art deep learning methods on three widely used PPIS prediction benchmarks. Besides, the results of ablation experiments demonstrated that the local features from spatially adjacent residues and global features from "remote" residues separately captured by EA-GCN and SA-RIM could benefit the model performance. Among them, the former was shown to have a more significant role in the PPIS prediction., (© 2024 Wiley Periodicals LLC.)

Abstract Background Protein-protein interactions (PPIs) play very important roles in diverse biological processes. Experimentally validated or predicted PPI data have become increasingly available in diverse plant species. To further explore the biological functions of PPIs, understanding the interaction details of plant PPIs (e.g., the 3D structural contexts of interaction sites) is necessary. By integrating bioinformatics algorithms, interaction details can be annotated at different levels and then compiled into user-friendly databases. In our previous study, we developed AraPPISite, which aimed to provide interaction site information for PPIs in the model plant Arabidopsis thaliana. Considering that the application of AraPPISite is limited to one species, it is very natural that AraPPISite should be evolved into a new database that can provide interaction details of PPIs in multiple plants. Description PlaPPISite (http://zzdlab.com/plappisite/index.php) is a comprehensive, high-coverage and interaction details-oriented database for 13 plant interactomes. In addition to collecting 121 experimentally verified structures of protein complexes, the complex structures of experimental/predicted PPIs in the 13 plants were also constructed, and the corresponding interaction sites were annotated. For the PPIs whose 3D structures could not be modelled, the associated domain-domain interactions (DDIs) and domain-motif interactions (DMIs) were inferred. To facilitate the reliability assessment of predicted PPIs, the source species of interolog templates, GO annotations, subcellular localizations and gene expression similarities are also provided. JavaScript packages were employed to visualize structures of protein complexes, protein interaction sites and protein interaction networks. We also developed an online tool for homology modelling and protein interaction site annotation of protein complexes. All data contained in PlaPPISite are also freely available on the Download page. Conclusion PlaPPISite provides the plant research community with an easy-to-use and comprehensive data resource for the search and analysis of protein interaction details from the 13 important plant species.

Background: Protein-protein interactions (PPIs) play very important roles in diverse biological processes. Experimentally validated or predicted PPI data have become increasingly available in diverse plant species. To further explore the biological functions of PPIs, understanding the interaction details of plant PPIs (e.g., the 3D structural contexts of interaction sites) is necessary. By integrating bioinformatics algorithms, interaction details can be annotated at different levels and then compiled into user-friendly databases. In our previous study, we developed AraPPISite, which aimed to provide interaction site information for PPIs in the model plant Arabidopsis thaliana. Considering that the application of AraPPISite is limited to one species, it is very natural that AraPPISite should be evolved into a new database that can provide interaction details of PPIs in multiple plants. Description: PlaPPISite (http://zzdlab.com/plappisite/index.php) is a comprehensive, high-coverage and interaction details-oriented database for 13 plant interactomes. In addition to collecting 121 experimentally verified structures of protein complexes, the complex structures of experimental/predicted PPIs in the 13 plants were also constructed, and the corresponding interaction sites were annotated. For the PPIs whose 3D structures could not be modelled, the associated domain-domain interactions (DDIs) and domain-motif interactions (DMIs) were inferred. To facilitate the reliability assessment of predicted PPIs, the source species of interolog templates, GO annotations, subcellular localizations and gene expression similarities are also provided. JavaScript packages were employed to visualize structures of protein complexes, protein interaction sites and protein interaction networks. We also developed an online tool for homology modelling and protein interaction site annotation of protein complexes. All data contained in PlaPPISite are also freely available on the Download page. Conclusion: PlaPPISite provides the plant research community with an easy-to-use and comprehensive data resource for the search and analysis of protein interaction details from the 13 important plant species. [ABSTRACT FROM AUTHOR]

Accurately pinpointing protein-protein interaction site (PPIS) on the molecular level is of utmost significance for annotating protein function and comprehending the mechanisms underpinning various diseases. While numerous computational methods for predicting PPIS have emerged, they have indeed mitigated the labor and time constraints associated with traditional experimental methods. However, the predictive accuracy of these methods has yet to reach the desired threshold. In this context, we proposed a groundbreaking graph-based computational model called GHGPR-PPIS. This innovative model leveraged a graph convolutional network using heat kernel (GraphHeat) in conjunction with Generalized PageRank techniques (GHGPR) to predict PPIS. Additionally, building upon the GHGPR framework, we devised an edge self-attention feature processing block, further augmenting the performance of the model. Experimental findings conclusively demonstrated that GHGPR-PPIS surpassed all competing state-of-the-art models when evaluated on the benchmark test set. Impressively, on two distinct independent test sets and a specific protein chain, GHGPR-PPIS consistently demonstrated superior generalization performance and practical applicability compared to the comparative model, AGAT-PPIS. Lastly, leveraging the t-SNE dimensionality reduction algorithm and clustering visualization technique, we delved into an interpretability analysis of the effectiveness of GHGPR-PPIS by meticulously comparing the outputs from different stages of the model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

PIPE () is a suite of four web servers for predicting a variety of folding- and binding-related properties of proteins. These include the solvent accessibility of amino acids upon protein folding, the amino acids forming the interfaces of protein-protein and protein-nucleic acid complexes, and the binding rate constants of these complexes. Three of the servers debuted in 2007, and have garnered ∼2,500 unique users and finished over 30,000 jobs. The functionalities of these servers are now enhanced, and a new sever, for predicting the binding rate constants, has been added. Together, these web servers form a pipeline from protein sequence to tertiary structure, then to quaternary structure, and finally to binding kinetics. [ABSTRACT FROM AUTHOR]

We describe a multi parametric-approach, YAPPIS-Finder, for predicting the PPI sites on protein surface. A non-redundant database of comprised of 2,265 protein-protein interaction interfaces (PPIIs) involving 4,530 protein-protein interacting partners (PPIPs) and depicting the interaction between protein-chains of experimentally determined PPCs was used in designing the YAPPIS-Finder. Parametric score obtained on analyzing these 4,530 PPIPs with respect to their residue interface propensity, their hydrophobic content, and amount of solvation free energy associated with them provided the basis of YAPPIS-Finder. By applying YAPPIS-Finder on another dataset 4,290 PPIPs from 2,145 PPIIs, the optimal range of the parametric scores and protein-probe van der Waals energy of interaction was determined. Subsequently, taking the optimal range of PPIP parametric scores and threshold for protein-probe van der Waals energy of interaction into the consideration, the YAPPIS-Finder was tested on a blind dataset of 554 protein-chains and it was found predicting 69.67% sites correctly. On predicting only one PPI site on each protein-chain, the YAPPIS-Finder found covering 22.91% of actually sites in the predicted site. Contrary to this, the sites predicted by SPPIDER covered 22.7% of actual sites. However, on predicting two PPI sites for each protein-chain, the percentage coverage of actual sites in the predicted sites by YAPPIS-Finder exceeded two-fold (i.e. 41.81%), thus making the YAPPIS-Finder a better method., (© 2022 Biomedical Informatics.)