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Identification of human immunodeficiency virus -1 E protein-targeting lead compounds by pharmacophore based screening

2022· article· en· W4311673765 on OpenAlexaff
Mazen Almehmadi, Alaa Shafie, Mamdouh Allahyani, Tahir Muhammad, Soukayna Baammi, Abdulelah Aljuaid, Abdulraheem Ali Almalki, Ahad Amer Alsaiari, Amal Adnan Ashour

Bibliographic record

VenueSaudi Medical Journal · 2022
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsCentre for Addiction and Mental Health
FundersTaif University
KeywordsPharmacophoreVirtual screeningDocking (animal)Human immunodeficiency virus (HIV)In silicoComputational biologyMedicineDrugCombinatorial chemistryVirologyStereochemistryPharmacologyBiochemistryBiologyChemistryGeneVeterinary medicine

Abstract

fetched live from OpenAlex

OBJECTIVES: To identify potential compounds by seeking the knowledge of molecular interactions between human immunodeficiency virus (HIV) glycoprotein (gp) 120 protein and anti-HIV drug (BMS-488043). METHODS: This study is a computational structure-based drug design study, carried out at University of Taif, Saudi Arabia and African Genome Centre (AGC), Mohammed VI Polytechnic University, Benguerir, Morocco from January 2021 to March 2022. Initially, using the docked structure of gp120 with BMS-488043, a structure-based pharmacophore model was created. The generated model was utilized for virtual screening of the ZINC and ChemBridge database in order to identify hit compounds. To further assess the time-dependent stability of the selected complexes, computer simulation was performed. RESULTS: From pharmacophore-based screening, 356 hits were obtained from both the database. The docking studies of the retrieved hit compounds reveal that all the compounds fit into the binding site of gp120. However, based on the significant interactions with the crucial residues and docking scores four compounds were suggested as potential hits. MD simulation of ChemBridge14695864 and ZINC06893293 in complex with gp120 suggested that both compounds significantly stabilized the receptor. CONCLUSION: These findings could aid in the design of effective drugs against HIV by inhibiting the interaction between gp120 and CD4.

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.

How this classification was reachedexpand

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)0.006
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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.881
Threshold uncertainty score0.814

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0060.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0000.001
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 head0.022
GPT teacher head0.329
Teacher spread0.307 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2022
Admission routes1
Has abstractyes

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