ArticleNature communications2022
A cryptic pocket in Ebola VP35 allosterically controls RNA binding.
Article in Nature communications, 2022. 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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Who cites it
26 citing papers in PubMed.
- Exploring the Structural Basis of Cryptic Pocket Formation Driven by Extensive Protein Conformational Changes in Drug Targets.Journal of chemical theory and computation · 2026Article
- Leveraging conformational ensembles in allosteric drug discovery.Trends in pharmacological sciences · 2026Review
- Decrypting cryptic pockets with physics-based simulations and artificial intelligence.Current opinion in structural biology · 2026Review
- Structure-based Discovery of a Non-competitive FTO Inhibitor Bound to a Cryptic Site at the Domain Interface.Journal of molecular biology · 2026Article
- Computational Ligand-Binding Site Prediction.Advances in experimental medicine and biology · 2026Review
- Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes.eLife · 2025Article
- Role of artificial intelligence in revolutionizing drug discovery.Fundamental research · 2025Review
- Discovering cryptic pocket opening and binding of a stimulant derivative in a vestibular site of the 5-HTScience advances · 2025Article
- Advances and Mechanisms of RNA-Ligand Interaction Predictions.Life (Basel, Switzerland) · 2025Review
- Adaptive sampling-based structural prediction reveals opening of a GABAScience advances · 2025Article
- Accounting for Fast vs Slow Exchange in Single Molecule FRET Experiments Reveals Hidden Conformational States.Journal of chemical theory and computation · 2024Article
- Accounting for fast vs slow exchange in single molecule FRET experiments reveals hidden conformational states.bioRxiv : the preprint server for biology · 2024Article
- G Protein Activation Occurs via a Largely Universal Mechanism.The journal of physical chemistry. B · 2024Article
- Toward physics-based precision medicine: Exploiting protein dynamics to design new therapeutics and interpret variants.Protein science : a publication of the Protein Society · 2024Review
- PopShift: A Thermodynamically Sound Approach to Estimate Binding Free Energies by Accounting for Ligand-Induced Population Shifts from a Ligand-Free Markov State Model.Journal of chemical theory and computation · 2024Article
- Article
- Folding@home: Achievements from over 20 years of citizen science herald the exascale era.Biophysical journal · 2023Review
- Accelerating Cryptic Pocket Discovery Using AlphaFold.Journal of chemical theory and computation · 2023Article
- Discovery of a cryptic pocket in the AI-predicted structure of PPM1D phosphatase explains the binding site and potency of its allosteric inhibitors.bioRxiv : the preprint server for biology · 2023Article
- Folding@home: achievements from over twenty years of citizen science herald the exascale era.ArXiv · 2023Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Protein-protein and protein-nucleic acid interactions are often considered difficult drug targets because the surfaces involved lack obvious druggable pockets. Cryptic pockets could present opportunities for targeting these interactions, but identifying and exploiting these pockets remains challenging. Here, we apply a general pipeline for identifying cryptic pockets to the interferon inhibitory domain (IID) of Ebola virus viral protein 35 (VP35). VP35 plays multiple essential roles in Ebola's replication cycle but lacks pockets that present obvious utility for drug design. Using adaptive sampling simulations and machine learning algorithms, we predict VP35 harbors a cryptic pocket that is allosterically coupled to a key dsRNA-binding interface. Thiol labeling experiments corroborate the predicted pocket and mutating the predicted allosteric network supports our model of allostery. Finally, covalent modifications that mimic drug binding allosterically disrupt dsRNA binding that is essential for immune evasion. Based on these results, we expect this pipeline will be applicable to other proteins.
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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.