ArticleNature chemistry2013
Snapshot of the equilibrium dynamics of a drug bound to HIV-1 reverse transcriptase.
Article in Nature chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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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Who cites it
45 citing papers in PubMed, 98 citations in OpenAlex.
- Garcinuntones A‒C, three new polyprenylated xanthones with cytotoxic and anti-HIV-1 activities from Garcinia nuntasaenii.Journal of natural medicines · 2026Article
- Discovery and molecular docking studies of nitrogen containing naphthyridine derivatives as potent HIV1 NNRTIs with anticancer potential.Scientific reports · 2025Article
- Development of enhanced HIV-1 non-nucleoside reverse transcriptase inhibitors with improved resistance and pharmacokinetic profiles.Science advances · 2025Article
- Unraveling Hydration Shell Dynamics and Viscosity Effects Around Cyanamide Probes via 2D IR Spectroscopy.Journal of the American Chemical Society · 2025Article
- Interplay between protease and reverse transcriptase dimerization in a model HIV-1 polyprotein.Protein science : a publication of the Protein Society · 2024Article
- Anti-Infective Activity ofAntibiotics (Basel, Switzerland) · 2024Article
- Small Molecule Drugs Targeting Viral Polymerases.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Anisotropic dynamics of an interfacial enzyme active site observed using tethered substrate analogs and ultrafast 2D IR spectroscopy.The Journal of chemical physics · 2023Article
- Cryogenic Single-Molecule Fluorescence Detection of the Mid-Infrared Response of an Intrinsic Pigment in a Light-Harvesting Complex.The journal of physical chemistry. B · 2023Article
- Halo Library, a Tool for Rapid Identification of Ligand Binding Sites on Proteins Using Crystallographic Fragment Screening.Journal of medicinal chemistry · 2023Article
- Targeting HIV-1 Reverse Transcriptase Using a Fragment-Based Approach.Molecules (Basel, Switzerland) · 2023Article
- Article
- Structural Basis of 2-Phenylamino-4-phenoxyquinoline Derivatives as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- HIV-1 gp120 Antagonists Also Inhibit HIV-1 Reverse Transcriptase by Bridging the NNRTI and NRTI Sites.Journal of medicinal chemistry · 2021Article
- Design, antihuman immunodeficiency activity and molecular docking studies of synthesized 2-aryl and 2-pyrimidinyl pyrrolidines.Molecular diversity · 2021Article
- Transparent window 2D IR spectroscopy of proteins.The Journal of chemical physics · 2021Review
- 2,4,5-Trisubstituted Pyrimidines as Potent HIV-1 NNRTIs: Rational Design, Synthesis, Activity Evaluation, and Crystallographic Studies.Journal of medicinal chemistry · 2021Article
- Avoiding Drug Resistance in HIV Reverse Transcriptase.Chemical reviews · 2021Review
- Multiple Target Drug Design Using LigBuilder 3.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV.Pharmaceuticals (Basel, Switzerland) · 2020Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The anti-AIDS drug rilpivirine undergoes conformational changes to bind HIV-1 reverse transcriptase (RT), which is an essential enzyme for the replication of HIV. These changes allow it to retain potency against mutations that otherwise would render the enzyme resistant. Here we report that water molecules play an essential role in this binding process. Femtosecond experiments and theory expose the molecular level dynamics of rilpivirine bound to HIV-1 RT. Two nitrile substituents, one on each arm of the drug, are used as vibrational probes of the structural dynamics within the binding pocket. Two-dimensional vibrational echo spectroscopy reveals that one nitrile group is unexpectedly hydrogen-bonded to a mobile water molecule, not identified in previous X-ray structures. Ultrafast nitrile-water dynamics are confirmed by simulations. A higher (1.51 Å) resolution X-ray structure also reveals a water-drug interaction network. Maintenance of a crucial anchoring hydrogen bond may help retain the potency of rilpivirine against pocket mutations despite the structural variations they cause.
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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.