ArticleeLife2023
Coevolution-based prediction of key allosteric residues for protein function regulation.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 30 citations in OpenAlex.
- A structure-aware generative AI framework for revealing functional relationships in protein families.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Allostery is a widespread cause of loss-of-function variant pathogenicity.Nature communications · 2026Article
- Computational approaches to druggable site identification: Current status and future perspective.Acta pharmaceutica Sinica. B · 2026Review
- Efficient Characterization of GPCRs Allosteric Modulation: Application to the Rational Design of De Novo S1PR1 Allosteric Modulators.Journal of chemical information and modeling · 2025Article
- Is SIRT3 and Mitochondria a Reliable Target for Parkinson's Disease and Aging? A Narrative Review.Molecular neurobiology · 2025Review
- Identifying a non-conserved site for achieving allosteric covalent inhibition of CECR2.Acta pharmacologica Sinica · 2025Article
- Decoding allosteric landscapes: computational methodologies for enzyme modulation and drug discovery.RSC chemical biology · 2025Review
- Importance of Inter-residue Contacts for Understanding Protein Folding and Unfolding Rates, Remote Homology, and Drug Design.Molecular biotechnology · 2025Review
- Revolutionizing Molecular Design for Innovative Therapeutic Applications through Artificial Intelligence.Molecules (Basel, Switzerland) · 2024Review
- Dissecting Allosteric Mutations for Antibiotic Resistance by Time-Dependent Linear Response Theory.Journal of chemical theory and computation · 2024Article
- A parameterized two-domain thermodynamic model explains diverse mutational effects on protein allostery.eLife · 2024Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- A parametrized two-domain thermodynamic model explains diverse mutational effects on protein allostery.bioRxiv : the preprint server for biology · 2024Article
- ASD2023: towards the integrating landscapes of allosteric knowledgebase.Nucleic acids research · 2024Article
- Exploring complexity of class-A Beta-lactamase family using physiochemical-based multiplex networks.Scientific reports · 2023Article
- Efficient enzymatic synthesis of chiral 2,3-dihydro-1,4-benzodioxane motif using engineeredRSC advances · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allostery is fundamental to many biological processes. Due to the distant regulation nature, how allosteric mutations, modifications, and effector binding impact protein function is difficult to forecast. In protein engineering, remote mutations cannot be rationally designed without large-scale experimental screening. Allosteric drugs have raised much attention due to their high specificity and possibility of overcoming existing drug-resistant mutations. However, optimization of allosteric compounds remains challenging. Here, we developed a novel computational method KeyAlloSite to predict allosteric site and to identify key allosteric residues (allo-residues) based on the evolutionary coupling model. We found that protein allosteric sites are strongly coupled to orthosteric site compared to non-functional sites. We further inferred key allo-residues by pairwise comparing the difference of evolutionary coupling scores of each residue in the allosteric pocket with the functional site. Our predicted key allo-residues are in accordance with previous experimental studies for typical allosteric proteins like BCR-ABL1, Tar, and PDZ3, as well as key cancer mutations. We also showed that KeyAlloSite can be used to predict key allosteric residues distant from the catalytic site that are important for enzyme catalysis. Our study demonstrates that weak coevolutionary couplings contain important information of protein allosteric regulation function. KeyAlloSite can be applied in studying the evolution of protein allosteric regulation, designing and optimizing allosteric drugs, and performing functional protein design and enzyme engineering.
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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 Socratic graph.