ArticleJournal of molecular biology2010
A dynamic model of HIV integrase inhibition and drug resistance.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 54 citations in OpenAlex.
- The AutoDock suite at 30.Protein science : a publication of the Protein Society · 2021Article
- Rigidity and flexibility characteristics of DD[E/D]-transposases Mos1 and Sleeping Beauty.Proteins · 2019Article
- Evaluation of novelMedChemComm · 2019Article
- Designing modulators of monoamine transporters using virtual screening techniques.Frontiers in pharmacology · 2015Review
- Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge.Journal of computer-aided molecular design · 2014Article
- Virtual screening with AutoDock Vina and the common pharmacophore engine of a low diversity library of fragments and hits against the three allosteric sites of HIV integrase: participation in the SAMPL4 protein-ligand binding challenge.Journal of computer-aided molecular design · 2014Article
- Blind prediction of HIV integrase binding from the SAMPL4 challenge.Journal of computer-aided molecular design · 2014Review
- Structural basis of Mos1 transposase inhibition by the anti-retroviral drug Raltegravir.ACS chemical biology · 2014Article
- Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants.Journal of medicinal chemistry · 2014Article
- Ligand access to the active site in Thermus thermophilus ba(3) and bovine heart aa(3) cytochrome oxidases.Biochemistry · 2013Article
- Oroxylin A inhibits hemolysis via hindering the self-assembly of α-hemolysin heptameric transmembrane pore.PLoS computational biology · 2013Article
- Probing chelation motifs in HIV integrase inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors.Chemical biology & drug design · 2012Article
- Structure-analysis of the HIV-1 integrase Y143C/R raltegravir resistance mutation in association with the secondary mutation T97A.Antimicrobial agents and chemotherapy · 2011Article
- Biomolecularmodeling and simulation: a field coming of age.Quarterly reviews of biophysics · 2011Review
- Molecular recognition in the case of flexible targets.Current pharmaceutical design · 2011Article
- Computer-aided drug-discovery techniques that account for receptor flexibility.Current opinion in pharmacology · 2010Review
- Structure-based modeling of the functional HIV-1 intasome and its inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Human immunodeficiency virus type 1 (HIV-1) integrase is one of three virally encoded enzymes essential for replication and, therefore, a rational choice as a drug target for the treatment of HIV-1-infected individuals. In 2007, raltegravir became the first integrase inhibitor approved for use in the treatment of HIV-infected patients, more than a decade since the approval of the first protease inhibitor (saquinavir, Hoffman La-Roche, 1995) and two decades since the approval of the first reverse transcriptase inhibitor (retrovir, GlaxoSmithKline, 1987). The slow progress toward a clinically effective HIV-1 integrase inhibitor can at least in part be attributed to a poor structural understanding of this key viral protein. Here we describe the development of a restrained molecular dynamics protocol that produces a more accurate model of the active site of this drug target. This model provides an advance on previously described models as it ensures that the catalytic DDE motif makes correct, monodentate interactions with the two active-site magnesium ions. Dynamic restraints applied to this coordination state create models with the correct solvation sphere for the metal ion complex and highlight the coordination sites available for metal-binding ligands. Application of appropriate dynamic flexibility to the core domain allowed the inclusion of multiple conformational states in subsequent docking studies. These models have allowed us to (1) explore the effects of key drug resistance mutations on the dynamic flexibility and conformational preferences of HIV integrase and to (2) study raltegravir binding in the context of these dynamic models of both wild type and the G140S/Q148H drug-resistant enzyme.
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.