ArticleScientific reports2015
Effects of drug-resistant mutations on the dynamic properties of HIV-1 protease and inhibition by Amprenavir and Darunavir.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed.
- Design, Synthesis, and Biological Evaluation of Darunavir Analogs as HIV-1 Protease Inhibitors.ACS bio & med chem Au · 2024Article
- FMO-guided design of darunavir analogs as HIV-1 protease inhibitors.Scientific reports · 2024Article
- 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
- Structural and functional insights into the DNA damage-inducible protein 1 (Ddi1) from protozoa.Current research in structural biology · 2022Article
- Predicted antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir can potentially bind to neutralize SARS-CoV-2 conserved proteins.Journal of biological research (Thessalonike, Greece) · 2021Article
- Deciphering Complex Mechanisms of Resistance and Loss of Potency through Coupled Molecular Dynamics and Machine Learning.Journal of chemical theory and computation · 2021Article
- Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch.Biomolecules · 2021Article
- Spontaneous Mutations in HIV-1 Gag, Protease, RT p66 in the First Replication Cycle and How They Appear: Insights from an In Vitro Assay on Mutation Rates and Types.International journal of molecular sciences · 2020Article
- Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations.The FEBS journal · 2020Article
- Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors.Retrovirology · 2020Article
- Inhibition of the activity of HIV-1 protease through antibody binding and mutations probed by molecular dynamics simulations.Scientific reports · 2020Article
- Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs.Molecules (Basel, Switzerland) · 2019Review
- Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations.Nucleic acids research · 2019Article
- 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
- Flap-site Fragment Restores Back Wild-type Behaviour in Resistant Form of HIV Protease.Molecular informatics · 2018Article
- Evolutionary footprint of epistasis.PLoS computational biology · 2018Article
- Crystal structure of the retroviral protease-like domain of a protozoal DNA damage-inducible 1 protein.FEBS open bio · 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
- Effect of polarization on HIV-1protease and fluoro-substituted inhibitors binding energies by large scale molecular dynamics simulations.Scientific reports · 2017Article
- Structural analyses of 2015-updated drug-resistant mutations in HIV-1 protease: an implication of protease inhibitor cross-resistance.BMC bioinformatics · 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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular dynamics simulations are performed to investigate the dynamic properties of wild-type HIV-1 protease and its two multi-drug-resistant variants (Flap + (L10I/G48V/I54V/V82A) and Act (V82T/I84V)) as well as their binding with APV and DRV inhibitors. The hydrophobic interactions between flap and 80 s (80's) loop residues (mainly I50-I84' and I50'-I84) play an important role in maintaining the closed conformation of HIV-1 protease. The double mutation in Act variant weakens the hydrophobic interactions, leading to the transition from closed to semi-open conformation of apo Act. APV or DRV binds with HIV-1 protease via both hydrophobic and hydrogen bonding interactions. The hydrophobic interactions from the inhibitor is aimed to the residues of I50 (I50'), I84 (I84'), and V82 (V82') which create hydrophobic core clusters to further stabilize the closed conformation of flaps, and the hydrogen bonding interactions are mainly focused with the active site of HIV-1 protease. The combined change in the two kinds of protease-inhibitor interactions is correlated with the observed resistance mutations. The present study sheds light on the microscopic mechanism underlying the mutation effects on the dynamics of HIV-1 protease and the inhibition by APV and DRV, providing useful information to the design of more potent and effective HIV-1 protease inhibitors.
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.