ArticleJournal of chemical information and modeling2012
A strategy based on protein-protein interface motifs may help in identifying drug off-targets.
Article in Journal of chemical information and modeling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- DiPPI: A Curated Data Set for Drug-like Molecules in Protein-Protein Interfaces.Journal of chemical information and modeling · 2024Article
- Conformational diversity and protein-protein interfaces in drug repurposing in Ras signaling pathway.Scientific reports · 2024Article
- Structural coverage of the human interactome.Briefings in bioinformatics · 2023Article
- Identifying Novel Drug Targets by iDTPnd: A Case Study of Kinase Inhibitors.Genomics, proteomics & bioinformatics · 2021Article
- Cryptochrome deletion in p53 mutant mice enhances apoptotic and anti-tumorigenic responses to UV damage at the transcriptome level.Functional & integrative genomics · 2019Article
- Methods for Discovering and Targeting Druggable Protein-Protein Interfaces and Their Application to Repurposing.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Oncoviruses Can Drive Cancer by Rewiring Signaling Pathways Through Interface Mimicry.Frontiers in oncology · 2019Article
- Prediction of Protein-compound Binding Energies from Known Activity Data: Docking-score-based Method and its Applications.Molecular informatics · 2018Article
- Quantitative Structure-activity Relationship (QSAR) Models for Docking Score Correction.Molecular informatics · 2017Article
- Modeling of RAS complexes supports roles in cancer for less studied partners.BMC biophysics · 2017Article
- Geomfinder: a multi-feature identifier of similar three-dimensional protein patterns: a ligand-independent approach.Journal of cheminformatics · 2016Article
- An integrated structure- and system-based framework to identify new targets of metabolites and known drugs.Bioinformatics (Oxford, England) · 2015Article
- Predicting the Effect of Mutations on Protein-Protein Binding Interactions through Structure-Based Interface Profiles.PLoS computational biology · 2015Article
- How do oncoprotein mutations rewire protein-protein interaction networks?Expert review of proteomics · 2015Review
- The structural pathway of interleukin 1 (IL-1) initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer.PLoS computational biology · 2014Article
- Non-redundant unique interface structures as templates for modeling protein interactions.PloS one · 2014Article
- The structural network of Interleukin-10 and its implications in inflammation and cancer.BMC genomics · 2014Article
- Genotype to phenotype via network analysis.Current opinion in genetics & development · 2013Review
- Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review.Pharmacology & therapeutics · 2013Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
Networks are increasingly used to study the impact of drugs at the systems level. From the algorithmic standpoint, a drug can "attack" nodes or edges of a protein-protein interaction network. In this work, we propose a new network strategy, "The Interface Attack", based on protein-protein interfaces. Similar interface architectures can occur between unrelated proteins. Consequently, in principle, a drug that binds to one has a certain probability of binding to others. The interface attack strategy simultaneously removes from the network all interactions that consist of similar interface motifs. This strategy is inspired by network pharmacology and allows inferring potential off-targets. We introduce a network model that we call "Protein Interface and Interaction Network (P2IN)", which is the integration of protein-protein interface structures and protein interaction networks. This interface-based network organization clarifies which protein pairs have structurally similar interfaces and which proteins may compete to bind the same surface region. We built the P2IN with the p53 signaling network and performed network robustness analysis. We show that (1) "hitting" frequent interfaces (a set of edges distributed around the network) might be as destructive as eleminating high degree proteins (hub nodes), (2) frequent interfaces are not always topologically critical elements in the network, and (3) interface attack may reveal functional changes in the system better than the attack of single proteins. In the off-target detection case study, we found that drugs blocking the interface between CDK6 and CDKN2D may also affect the interaction between CDK4 and CDKN2D.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.