Evidence map›Paper›PMID 27587008›Full record

ArticleBMC bioinformatics2016

Modeling the functional state of the reverse transcriptase of hepatitis B virus and its application to probing drug-protein interaction.

Xiaojun Xu, Hong Thai, Kathryn M Kitrinos, Guoliang Xia, Anuj Gaggar, Matthew Paulson, Lilia Ganova-Raeva, Yury Khudyakov, James Lara

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC bioinformatics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 15 citations in OpenAlex.

  1. Small Molecule Drugs Targeting Viral Polymerases.Pharmaceuticals (Basel, Switzerland) · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Xiaojun XuDivision of Viral Hepatitis, National Center for HIV, Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA.
Hong ThaiDivision of Viral Hepatitis, National Center for HIV, Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA.
Kathryn M KitrinosGilead Sciences, Inc., Foster City, CA, USA.
Guoliang XiaDivision of Viral Hepatitis, National Center for HIV, Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA.
Anuj GaggarGilead Sciences, Inc., Foster City, CA, USA.
Matthew PaulsonGilead Sciences, Inc., Foster City, CA, USA.
Lilia Ganova-RaevaDivision of Viral Hepatitis, National Center for HIV, Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA.
Yury KhudyakovDivision of Viral Hepatitis, National Center for HIV, Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA.
James LaraDivision of Viral Hepatitis, National Center for HIV, Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. xzl5@cdc.gov.
Centers for Disease Control and Prevention · USGilead Sciences (United States) · USNational Center for HIV/AIDS Viral Hepatitis STD and TB Prevention · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHerein, the predicted atomic structures of five representative sequence variants of the reverse transcriptase protein (RT) of hepatitis B virus (HBV), sampled from patients with rapid or slow response to tenofovir disoproxil fumarate (TDF) treatment, have been examined to identify structural variations between them in order to assess structural and functional properties of HBV-RT variants associated with the differential responses to TDF treatment.

resultsWe utilized a hybrid computational approach to model the atomistic structures of HBV-RT/DNA-RNA/dATP and HBV-RT/DNA-RNA/TFV-DP (tenofovir diphosphate) complexes with the native hybrid DNA-RNA substrate in place. Multi-nanosecond molecular dynamics (MD) simulations of HBV-RT/DNA-RNA/dATP complexes revealed strong coupling of the natural nucleotide substrate, dATP, to the active site of the RT, and the differential involvement of the two putative magnesium cations (Mg(2+)) at the active site, whereby one Mg(2+) directly bridges the interaction between dATP and HBV-RT and the other serves as a coordinator to maintain an optimal configuration of the active site. Solvated interaction energy (SIE) calculated in MD simulations of HBV-RT/DNA-RNA/TFV-DP complexes indicate no differential binding affinity between TFV-DP and HBV-RT variants identified in patients with slow or rapid response to TDF treatment.

conclusionThe predicted atomic structures accurately represent functional states of HBV-RT. The equivalent interaction between TFV-DP and each examined HBV-RT variants suggests that binding affinity of TFV-DP to HBV-RT is not associated with delayed viral clearance.

Indexed as

Drug InteractionsModels, MolecularAntiviral AgentsCatalytic DomainDrug Resistance, ViralHepatitis B virusHumansIonsMagnesiumReverse Transcriptase InhibitorsRNA-Directed DNA PolymeraseTenofovirThermodynamicsViral ProteinsAntiviral AgentsIonsMagnesiumReverse Transcriptase InhibitorsRNA-Directed DNA PolymeraseTenofovirViral ProteinsDrug resistanceHepatitis BHybrid structure modelingMolecular dynamics (MD)Reverse transcriptaseSolvated interaction energy (SIE)Tenofovir

Identifiers

PMID27587008
PMCPMC5009823
OpenAlexW2512136612

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.