GitHub - madhubioinformatics/G6PD-activators-Machine-learning: Glucose-6-Phosphate Dehydrogenase (G6PD) is a ubiquitous cytoplasmic enzyme converting glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway (PPP). The G6PD deficiency renders the inability to regenerate glutathione due to lack of NADPH and produces the oxidative injury in retina that accelerate the dystrophic conditions to photoreceptor cells and damage the retinal blood barrier function. In this study, we constructed pharmacophore-based models based on the compound complex of G6PD with AG1 (G6PD activator) followed by virtual screening. 53 hit molecules were mapped with core pharmacophore features. We calculated molecular descriptors, clustering, principle component analysis (PCA) to pharmacophore hit molecules and further applied statistical machine learning methods . Results showed that the all model performed best and classified as drug-like (18) and nondrug-like (35) compounds. The drug-like compounds were further evaluated our established cheminformatics pipeline (molecular docking and in silico ADMET analysis). Finally, five hits with different scaffolds were picked out for docking studies and in silico ADMET analysis. This study proposes that the combination of machine learning methods with traditional structure-based virtual screening can effectively strengthen the ability in finding potential G6PD activators designing for G6PD deficiency diseases. Moreover, these compounds can be considered as safe agents for further validation studies at cell level, animal model, and even clinic setting.

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AMDET_properites of 53 compounds_Table3.xlsx	AMDET_properites of 53 compounds_Table3.xlsx
Activesite_castp.tif	Activesite_castp.tif
Alignment1.tif	Alignment1.tif
Fig. 4.tif	Fig. 4.tif
Fig. 5.tif	Fig. 5.tif
Fig.1.tif	Fig.1.tif
Fig.2.tif	Fig.2.tif
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Fig.8.tif	Fig.8.tif
Fig4.tif	Fig4.tif
Fig5.tif	Fig5.tif
Graphical abstract.tif	Graphical abstract.tif
Heatmap_descriptors.xlsx	Heatmap_descriptors.xlsx
ML_results.xlsx	ML_results.xlsx
Pharmacophore1.tif	Pharmacophore1.tif
Pharmacophore2.tif	Pharmacophore2.tif
Pharmacophore_53 hits_1.tif	Pharmacophore_53 hits_1.tif
Pharmacophore_complex.pdb	Pharmacophore_complex.pdb
Pharmacopore_hits_1-9.tif	Pharmacopore_hits_1-9.tif
Pharmacopore_hits_10-18.tif	Pharmacopore_hits_10-18.tif
Pharmacopore_hits_19-27.tif	Pharmacopore_hits_19-27.tif
Pharmacopore_hits_28-36.tif	Pharmacopore_hits_28-36.tif
Pharmacopore_hits_37-45.tif	Pharmacopore_hits_37-45.tif
Pharmacopore_hits_46-53.tif	Pharmacopore_hits_46-53.tif
R-program.txt	R-program.txt
README.md	README.md
SWISS-ADMET of top 5 compounds_Table2.xlsx	SWISS-ADMET of top 5 compounds_Table2.xlsx
Taining set_S2_Table.docx	Taining set_S2_Table.docx
Test set_S1_Table.docx	Test set_S1_Table.docx

Name

Last commit message

Last commit date

6 Commits

AMDET_properites of 53 compounds_Table3.xlsx

Graphical abstract.tif

Heatmap_descriptors.xlsx

ML_results.xlsx

Pharmacophore1.tif

Pharmacophore2.tif

Pharmacophore_53 hits_1.tif

Pharmacophore_complex.pdb

Pharmacopore_hits_1-9.tif

Pharmacopore_hits_10-18.tif

Pharmacopore_hits_19-27.tif

Pharmacopore_hits_28-36.tif

Pharmacopore_hits_37-45.tif

Pharmacopore_hits_46-53.tif

R-program.txt

README.md

SWISS-ADMET of top 5 compounds_Table2.xlsx

Taining set_S2_Table.docx

Test set_S1_Table.docx

#Discovery of small molecule activators for G6PD (glucose-6-phosphate dehydrogenase) using machine learning approaches

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Glucose-6-Phosphate Dehydrogenase (G6PD) is a ubiquitous cytoplasmic enzyme converting glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway (PPP). The G6PD deficiency renders the inability to regenerate glutathione due to lack of NADPH and produces the oxidative injury in retina that accelerate the dystrophic conditions t…

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