ArticleProteins2008
Evaluating the potency of HIV-1 protease drugs to combat resistance.
Article in Proteins, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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.
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Who cites it
36 citing papers in PubMed, 118 citations in OpenAlex.
- Multi-Epitopic Peptide Vaccine Against Newcastle Disease Virus: Molecular Dynamics Simulation and Experimental Validation.Vaccines · 2024Article
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- FMO-guided design of darunavir analogs as HIV-1 protease inhibitors.Scientific reports · 2024Article
- Binding selectivity-dependent molecular mechanism of inhibitors towards CDK2 and CDK6 investigated by multiple short molecular dynamics and free energy landscapes.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Engineering human JMJD2A tudor domains for an improved understanding of histone peptide recognition.Proteins · 2023Article
- Systematic analysis and molecular profiling of EGFR allosteric inhibitor cross-reactivity across the proto-oncogenic ErbB family kinases by integrating dynamics simulation, energetics calculation and biochemical assay.European biophysics journal : EBJ · 2022Article
- Article
- Deciphering Complex Mechanisms of Resistance and Loss of Potency through Coupled Molecular Dynamics and Machine Learning.Journal of chemical theory and computation · 2021Article
- Mechanistic analysis of A46V, H57Y, and D129N in pyrazinamidase associated with pyrazinamide resistance.Saudi journal of biological sciences · 2020Article
- Pyrazinamide resistance of novel mutations inRSC advances · 2020Article
- Effective estimation of the inhibitor affinity of HIV-1 proteaseRSC advances · 2020Article
- Gibbs Free Energy Calculation of Mutation in PncA and RpsA Associated With Pyrazinamide Resistance.Frontiers in molecular biosciences · 2020Article
- Structural and free energy landscape of novel mutations in ribosomal protein S1 (rpsA) associated with pyrazinamide resistance.Scientific reports · 2019Article
- Structural Dynamics Behind Clinical Mutants of PncA-Asp12Ala, Pro54Leu, and His57Pro ofFrontiers in bioengineering and biotechnology · 2019Article
- Importance of Incorporating Protein Flexibility in Molecule Modeling: A Theoretical Study on Type IFrontiers in pharmacology · 2019Article
- The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction.Structural dynamics (Melville, N.Y.) · 2018Article
- Dynamics revelation of conformational changes and binding modes of heat shock protein 90 induced by inhibitor associations.RSC advances · 2018Article
- Effect of polarization on HIV-1protease and fluoro-substituted inhibitors binding energies by large scale molecular dynamics simulations.Scientific reports · 2017Article
- Revealing origin of decrease in potency of darunavir and amprenavir against HIV-2 relative to HIV-1 protease by molecular dynamics simulations.Scientific reports · 2014Article
- Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics.BMC genomics · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1 protease has been an important drug target for the antiretroviral treatment of HIV infection. The efficacy of protease drugs is impaired by the rapid emergence of resistant virus strains. Understanding the molecular basis and evaluating the potency of an inhibitor to combat resistance are no doubt important in AIDS therapy. In this study, we first identified residues that have significant contributions to binding with six substrates using molecular dynamics simulations and Molecular Mechanics Generalized Born Surface Area calculations. Among the critical residues, Asp25, Gly27, Ala28, Asp29, and Gly49 are well conserved, with which the potent drugs should form strong interactions. We then calculated the contribution of each residue to binding with eight FDA approved drugs. We analyzed the conservation of each protease residue and also compared the interaction between the HIV protease and individual residues of the drugs and substrates. Our analyses showed that resistant mutations usually occur at less conserved residues forming more favorable interactions with drugs than with substrates. To quantitatively integrate the binding free energy and conservation information, we defined an empirical parameter called free energy/variability (FV) value, which is the product of the contribution of a single residue to the binding free energy and the sequence variability at that position. As a validation, the FV value was shown to identify single resistant mutations with an accuracy of 88%. Finally, we evaluated the potency of a newly approved drug, darunavir, to combat resistance and predicted that darunavir is more potent than amprenavir but may be susceptible to mutations on Val32 and Ile84.
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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.