ArticleJournal of molecular biology2012
Modulating protein-protein interactions with small molecules: the importance of binding hotspots.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 70 citations in OpenAlex.
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- Active Stacking-Deep Learning with Strategic Sampling for Small and Imbalanced Chemical Toxicity Prediction.ACS omega · 2025Article
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- Structural modulation of insulin by hydrophobic and hydrophilic molecules.RSC advances · 2023Article
- QuoteTarget: A sequence-based transformer protein language model to identify potentially druggable protein targets.Protein science : a publication of the Protein Society · 2023Article
- Pathogen-driven cancers from a structural perspective: Targeting host-pathogen protein-protein interactions.Frontiers in oncology · 2023Review
- Leveraging the multivalent p53 peptide-MdmX interaction to guide the improvement of small molecule inhibitors.Nature communications · 2022Article
- Synaptic Secretion and Beyond: Targeting Synapse and Neurotransmitters to Treat Neurodegenerative Diseases.Oxidative medicine and cellular longevity · 2022Review
- Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials.Signal transduction and targeted therapy · 2020Review
- Allosteric Binding Sites On Nuclear Receptors: Focus On Drug Efficacy and Selectivity.International journal of molecular sciences · 2020Article
- Characterization and Validation of Arg286 Residue of IL-1RAcP as a Potential Drug Target for Osteoarthritis.Frontiers in chemistry · 2020Article
- Investigation of protein-protein interactions and hot spot region between PD-1 and PD-L1 by fragment molecular orbital method.Scientific reports · 2019Article
- Methods for Discovering and Targeting Druggable Protein-Protein Interfaces and Their Application to Repurposing.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Functional expression and impact of testis-specific gene antigen 10 in breast cancer: a combined in vitro and in silico analysis.BioImpacts : BI · 2019Article
- RMut: R package for a Boolean sensitivity analysis against various types of mutations.PloS one · 2019Article
- Mimicry of a β-Hairpin Turn by a Nonpeptidic Laterally Flexible Foldamer.Organic letters · 2018Article
- The design of high affinity human PD-1 mutants by using molecular dynamics simulations (MD).Cell communication and signaling : CCS · 2018Article
- Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Drug-Like Protein-Protein Interaction Modulators: Challenges and Opportunities for Drug Discovery and Chemical Biology.Molecular informatics · 2014Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The modulation of protein-protein interactions (PPIs) by small drug-like molecules is a relatively new area of research and has opened up new opportunities in drug discovery. However, the progress made in this area is limited to a handful of known cases of small molecules that target specific diseases. With the increasing availability of protein structure complexes, it is highly important to devise strategies exploiting homologous structure space on a large scale for discovering putative PPIs that could be attractive drug targets. Here, we propose a scheme that allows performing large-scale screening of all protein complexes and finding putative small-molecule and/or peptide binding sites overlapping with protein-protein binding sites (so-called "multibinding sites"). We find more than 600 nonredundant proteins from 60 protein families with multibinding sites. Moreover, we show that the multibinding sites are mostly observed in transient complexes, largely overlap with the binding hotspots and are more evolutionarily conserved than other interface sites. We investigate possible mechanisms of how small molecules may modulate protein-protein binding and discuss examples of new candidates for drug design.
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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.