ArticleJournal of chemical theory and computation2012
Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation.
Article in Journal of chemical theory and computation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Conformational asymmetry of human immunodeficiency virus-1 protease flaps increases along the darunavir drug resistance pathway.Protein science : a publication of the Protein Society · 2026Article
- Ligand Versatility and Resistance Mechanism of Monotherapy-Grade HIV-1 Protease Inhibitor GRL-142 Binding the Multidrug Resistant Variant p51: Insights from 1 μs MD Simulations.Journal of chemical information and modeling · 2026Article
- Dynamic Allostery: Evolution's Double-Edged Sword in Protein Function and Disease.Journal of molecular biology · 2025Review
- Experimental spectra, electronic properties (liquid and gaseous phases) and activity against SARS-CoV-2 main protease of Fluphenazine dihydrochloride: DFT and MD simulations.Journal of molecular structure · 2022Article
- The structural, dynamic, and thermodynamic basis of darunavir resistance of a heavily mutated HIV-1 protease using molecular dynamics simulation.Frontiers in molecular biosciences · 2022Article
- Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond.Chemical reviews · 2021Review
- Structural Impacts of Drug-Resistance Mutations Appearing in HIV-2 Protease.Molecules (Basel, Switzerland) · 2021Article
- Viral proteases: Structure, mechanism and inhibition.The Enzymes · 2021Article
- NMR and MD studies combined to elucidate inhibitor and water interactions of HIV-1 protease and their modulations with resistance mutations.Journal of biomolecular NMR · 2019Article
- An NMR strategy to detect conformational differences in a protein complexed with highly analogous inhibitors in solution.Methods (San Diego, Calif.) · 2018Article
- Hydration Structure and Dynamics of Inhibitor-Bound HIV-1 Protease.Journal of chemical theory and computation · 2018Article
- Replica Exchange Gaussian Accelerated Molecular Dynamics: Improved Enhanced Sampling and Free Energy Calculation.Journal of chemical theory and computation · 2018Article
- Probing Structural Changes among Analogous Inhibitor-Bound Forms of HIV-1 Protease and a Drug-Resistant Mutant in Solution by Nuclear Magnetic Resonance.Biochemistry · 2018Article
- Ligand Binding Pathways and Conformational Transitions of the HIV Protease.Biochemistry · 2018Article
- Interdependence of Inhibitor Recognition in HIV-1 Protease.Journal of chemical theory and computation · 2017Article
- Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K.Journal of medicinal chemistry · 2017Article
- Mechanism of the Association Pathways for a Pair of Fast and Slow Binding Ligands of HIV-1 Protease.Biochemistry · 2017Article
- Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease.Journal of molecular biology · 2016Article
- Improving Viral Protease Inhibitors to Counter Drug Resistance.Trends in microbiology · 2016Review
- Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance.Frontiers in microbiology · 2016Article
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 2 institutions in 1 country.
Funding
Abstract
In the rapidly evolving disease of HIV drug resistance readily emerges, nullifying the effectiveness of therapy. Drug resistance has been extensively studied in HIV-1 protease where resistance occurs when the balance between enzyme inhibition and substrate recognition and turn-over is perturbed to favor catalytic activity. Mutations which confer drug resistance can impact the dynamics and structure of both the bound and unbound forms of the enzyme. Flap+ is a multi-drug-resistant variant of HIV-1 protease with a combination of mutations at the edge of the active site, within the active site, and in the flaps (L10I, G48V, I54V, V82A). The impact of these mutations on the dynamics in the unliganded form in comparison with the wild-type protease was elucidated with Molecular Dynamic simulations and NMR relaxation experiments. The comparative analyses from both methods concur in showing that the enzyme's dynamics are impacted by the drug resistance mutations in Flap+ protease. These alterations in the enzyme dynamics, particularly within the flaps, likely modulate the balance between substrate turn-over and drug binding, thereby conferring drug resistance.
Identifiers
What OpenQuestion holds
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.