ArticleJournal of the American Chemical Society2014
Drug resistance conferred by mutations outside the active site through alterations in the dynamic and structural ensemble of HIV-1 protease.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 105 citations in OpenAlex.
- Advancements in development of novel class of HIV protease inhibitors.Annals of medicine · 2026Review
- Rhomboid Proteases in Plasmodium spp. : Biology, Functional Roles, and Therapeutic Potential.Acta parasitologica · 2026Review
- Protein language model embeddings improve HIV drug resistance prediction: a comprehensive benchmark with attention-based interpretability.Bioinformatics (Oxford, England) · 2026Article
- Predicting the Impact of Drug Resistance Mutations on Inhibitor Potency with Molecular Dynamics and Machine Learning.The journal of physical chemistry. B · 2025Article
- Secreted retropepsin-like enzymes are essential for stress tolerance and biofilm formation inmBio · 2025Article
- Enzyme-substrate co-display on yeast empowers engineering of tobacco etch virus protease activity.Protein engineering, design & selection : PEDS · 2025Article
- Kinetic coevolutionary models predict the temporal emergence of HIV-1 resistance mutations under drug selection pressure.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2.Nature communications · 2024Article
- Evolution of drug resistance drives destabilization of flap region dynamics in HIV-1 protease.Biophysical reports · 2023Article
- Evolving Mutational Buildup in HIV-1 Protease Shifts Conformational Dynamics to Gain Drug Resistance.Journal of chemical information and modeling · 2023Article
- Comprehending the Structure, Dynamics, and Mechanism of Action of Drug-Resistant HIV Protease.ACS omega · 2023Review
- Article
- Computational Insights into the Allosteric Modulation of a Phthalate-Degrading Hydrolase by Distal Mutations.Biomolecules · 2023Article
- Understanding Drug Resistance of Wild-Type and L38HL Insertion Mutant of HIV-1 C Protease to Saquinavir.Genes · 2023Article
- Activity-based CRISPR scanning uncovers allostery in DNA methylation maintenance machinery.eLife · 2023Article
- HIV-1 protease with 10 lopinavir and darunavir resistance mutations exhibits altered inhibition, structural rearrangements and extreme dynamics.Journal of molecular graphics & modelling · 2022Article
- Sequence dependencies and biophysical features both govern cleavage of diverse cut-sites by HIV protease.Protein science : a publication of the Protein Society · 2022Article
- An intermolecular salt bridge linking substrate binding and P1 substrate specificity switch of arterivirus 3C-like proteases.Computational and structural biotechnology journal · 2022Article
- Elasticity-Associated Functionality and Inhibition of the HIV Protease.Advances in experimental medicine and biology · 2022Article
- Deciphering Complex Mechanisms of Resistance and Loss of Potency through Coupled Molecular Dynamics and Machine Learning.Journal of chemical theory and computation · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
HIV-1 protease inhibitors are part of the highly active antiretroviral therapy effectively used in the treatment of HIV infection and AIDS. Darunavir (DRV) is the most potent of these inhibitors, soliciting drug resistance only when a complex combination of mutations occur both inside and outside the protease active site. With few exceptions, the role of mutations outside the active site in conferring resistance remains largely elusive. Through a series of DRV-protease complex crystal structures, inhibition assays, and molecular dynamics simulations, we find that single and double site mutations outside the active site often associated with DRV resistance alter the structure and dynamic ensemble of HIV-1 protease active site. These alterations correlate with the observed inhibitor binding affinities for the mutants, and suggest a network hypothesis on how the effect of distal mutations are propagated to pivotal residues at the active site and may contribute to conferring drug resistance.
Indexed as
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.