MétaCan
Menu
Back to cohort
Record W2167186042 · doi:10.1002/prot.20455

Quantum study of mutational effect in binding of efavirenz to HIV‐1 RT

2005· article· en· W2167186042 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueProteins Structure Function and Bioinformatics · 2005
Typearticle
Languageen
FieldMedicine
TopicHIV/AIDS drug development and treatment
Canadian institutionsMinistry of Education and Child Care
Fundersnot available
KeywordsEfavirenzChemistryMutantBinding energyAb initioInteraction energyConformational changeReverse transcriptaseResidue (chemistry)Human immunodeficiency virus (HIV)StereochemistryBiologyBiochemistryPhysicsVirologyMoleculeAtomic physicsRNA

Abstract

fetched live from OpenAlex

Full quantum mechanical computational study has been carried out to study binding of efavirenz (EFZ), a second generation FDA approved nonnucleoside inhibitor, to HIV-1 reverse transcriptase (RT) and its K103N and Y181C mutants using the MFCC (molecular fractionation with conjugate caps) method. The binding interaction energies between EFZ and each protein fragment are calculated using a combination of HF/3-21G, B3LYP/6-31G* and MP2/6-31G* ab initio levels. The present computation shows that Efavirenz binds to HIV-1 RT predominantly through strong electrostatic interaction with the Lys101 residue. The small loss of binding to K103N mutant by Efavirenz can be attributed to a slightly weakened attractive interaction between the drug and Lys101 due to a conformational change of mutation. The small loss of binding to Y181C mutant by efavirenz can be attributed to the Glu698 residue moving closer to EFZ due to conformational change, which results in an increase of repulsive energy relative to the wild type (WT). The binding of efavirenz-derived DPC961 to HIV-1 RT is enhanced by an additional attractive interaction to residue Hid235 and reduced repulsion to Glu698, resulting in an increase of binding energy by about 4 kcal/mol.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.161
Threshold uncertainty score0.349

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.246
Teacher spread0.238 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it