ReviewCurrent pharmaceutical design2014
Druggable orthosteric and allosteric hot spots to target protein-protein interactions.
Review in Current pharmaceutical design, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
The trial behind it
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
20 citing papers in PubMed, 46 citations in OpenAlex.
- Designing Cyclic-Constrained Peptides to Inhibit Human Phosphoglycerate Dehydrogenase.Molecules (Basel, Switzerland) · 2023Article
- A Cancer Cell-Intrinsic GOT2-PPARδ Axis Suppresses Antitumor Immunity.Cancer discovery · 2022Article
- Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein-Protein Interactions.The journal of physical chemistry. B · 2022Article
- In Silico Insights towards the Identification of SARS-CoV-2 NSP13 Helicase Druggable Pockets.Biomolecules · 2022Article
- Allosteric Site of ACE-2 as a Drug Target for COVID-19.ACS pharmacology & translational science · 2022Article
- The Allosteric Effect in Antibody-Antigen Recognition.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Supertertiary protein structure affects an allosteric network.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Mapping of the FGF14:Nav1.6 complex interface reveals FLPK as a functionally active peptide modulating excitability.Physiological reports · 2020Article
- Monte Carlo simulations using PELE to identify a protein-protein inhibitor binding site and pose.RSC advances · 2020Article
- Article
- RMut: R package for a Boolean sensitivity analysis against various types of mutations.PloS one · 2019Article
- A structural study of the complex between neuroepithelial cell transforming gene 1 (Net1) and RhoA reveals a potential anticancer drug hot spot.The Journal of biological chemistry · 2018Article
- Molecular Dynamics Simulations and Dynamic Network Analysis Reveal the Allosteric Unbinding of Monobody to H-Ras Triggered by R135K Mutation.International journal of molecular sciences · 2017Article
- Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell.Chemical reviews · 2016Review
- Emerging Computational Methods for the Rational Discovery of Allosteric Drugs.Chemical reviews · 2016Review
- Adaptability of protein structures to enable functional interactions and evolutionary implications.Current opinion in structural biology · 2015Review
- How an Inhibitor Bound to Subunit Interface Alters Triosephosphate Isomerase Dynamics.Biophysical journal · 2015Article
- Developing multi-target therapeutics to fine-tune the evolutionary dynamics of the cancer ecosystem.Frontiers in pharmacology · 2015Article
- Investigation of the interactions between the EphB2 receptor and SNEW peptide variants.Growth factors (Chur, Switzerland) · 2014Article
- 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
2 authors at 1 institution in 1 country.
Funding
Abstract
Drug designing targeting protein-protein interactions is challenging. Because structural elucidation and computational analysis have revealed the importance of hot spot residues in stabilizing these interactions, there have been on-going efforts to develop drugs which bind the hot spots and out-compete the native protein partners. The question arises as to what are the key 'druggable' properties of hot spots in protein-protein interactions and whether these mimic the general hot spot definition. Identification of orthosteric (at the protein- protein interaction site) and allosteric (elsewhere) druggable hot spots is expected to help in discovering compounds that can more effectively modulate protein-protein interactions. For example, are there any other significant features beyond their location in pockets in the interface? The interactions of protein-protein hot spots are coupled with conformational dynamics of protein complexes. Currently increasing efforts focus on the allosteric drug discovery. Allosteric drugs bind away from the native binding site and can modulate the native interactions. We propose that identification of allosteric hot spots could similarly help in more effective allosteric drug discovery. While detection of allosteric hot spots is challenging, targeting drugs to these residues has the potential of greatly increasing the hot spot and protein druggability.
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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.