ArticlePLoS computational biology2018
Reversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 88 citations in OpenAlex.
- Residue Interaction Network Reveals Allosteric Pathways Linking Orthosteric and Intracellular Sites in Class A GPCRs.Journal of chemical information and modeling · 2026Article
- Inactivation Switch for Run-up in TRPV2.Research square · 2026Article
- MAVISp: A modular structure-based framework for protein variant effects.Protein science : a publication of the Protein Society · 2026Article
- Physics Determines and Evolution Shapes Basic Units of Protein Function and Allosteric Regulation.Methods in molecular biology (Clifton, N.J.) · 2026Review
- How residence time works in allosteric drugs.Current opinion in structural biology · 2025Review
- Protein Catalysis Through Structural Dynamics: A Comprehensive Analysis of Energy Conversion in Enzymatic Systems and Its Computational Limitations.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Protein allosteric site identification using machine learning and per amino acid residue reported internal protein nanoenvironment descriptors.Computational and structural biotechnology journal · 2024Article
- Toward the Design of Allosteric Effectors: Gaining Comprehensive Control of Drug Properties and Actions.Journal of medicinal chemistry · 2024Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- ASD2023: towards the integrating landscapes of allosteric knowledgebase.Nucleic acids research · 2024Article
- Article
- Markov State Models and Perturbation-Based Approaches Reveal Distinct Dynamic Signatures and Hidden Allosteric Pockets in the Emerging SARS-Cov-2 Spike Omicron Variant Complexes with the Host Receptor: The Interplay of Dynamics and Convergent Evolution Modulates Allostery and Functional Mechanisms.Journal of chemical information and modeling · 2023Article
- AlloReverse: multiscale understanding among hierarchical allosteric regulations.Nucleic acids research · 2023Article
- Machine learning and protein allostery.Trends in biochemical sciences · 2023Review
- Exploring and Learning the Universe of Protein Allostery Using Artificial Intelligence Augmented Biophysical and Computational Approaches.Journal of chemical information and modeling · 2023Review
- AlloMAPS 2: allosteric fingerprints of the AlphaFold and Pfam-trRosetta predicted structures for engineering and design.Nucleic acids research · 2023Article
- A Structure-Based Allosteric Modulator Design Paradigm.Health data science · 2023Review
- Probing Mechanisms of Binding and Allostery in the SARS-CoV-2 Spike Omicron Variant Complexes with the Host Receptor: Revealing Functional Roles of the Binding Hotspots in Mediating Epistatic Effects and Communication with Allosteric Pockets.International journal of molecular sciences · 2022Article
- Allosteric Hotspots in the Main Protease of SARS-CoV-2.Journal of molecular biology · 2022Article
- A catalytic dyad modulates conformational change in the COThe Journal of biological chemistry · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The omnipresence of allosteric regulation together with the fundamental role of structural dynamics in this phenomenon have initiated a great interest to the detection of regulatory exosites and design of corresponding effectors. However, despite a general consensus on the key role of dynamics most of the earlier efforts on the prediction of allosteric sites are heavily crippled by the static nature of the underlying methods, which are either structure-based approaches seeking for deep surface pockets typical for "traditional" orthosteric drugs or sequence-based techniques exploiting the conservation of protein sequences. Because of the critical role of global protein dynamics in allosteric signaling, we investigate the hypothesis of reversibility in allosteric communication, according to which allosteric sites can be detected via the perturbation of the functional sites. The reversibility is tested here using our structure-based perturbation model of allostery, which allows one to analyze the causality and energetics of allosteric communication. We validate the "reverse perturbation" hypothesis and its predictive power on a set of classical allosteric proteins, then, on the independent extended benchmark set. We also show that, in addition to known allosteric sites, the perturbation of the functional sites unravels rather extended protein regions, which can host latent regulatory exosites. These protein parts that are dynamically coupled with functional sites can also be used for inducing and tuning allosteric communication, and an exhaustive exploration of the per-residue contributions to allosteric effects can eventually lead to the optimal modulation of protein activity. The site-effector interactions necessary for a specific mode and level of allosteric communication can be fine-tuned by adjusting the site's structure to an available effector molecule and by the design or selection of an appropriate ligand.
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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.