دراسة نظرية حاسوبية لتأثير المركبات الطبيعية على إنزيم 14-ألفا-ديميثيلاز كاستراتيجية علاجية ضد داء الفطار المخاطي

هاني سليم; ثناء مراد; عبير المصري; إلهام المحمد; خلود محمد; ظبية خلوف

doi:10.5281/zenodo.21788863

Authors

Dr. Hani Salim Al Wataniya Private University
Thanaa Mourad Al Wataniya Private University
Abeer Almasri Al Wataniya Private University
Elham Mohammed Al Wataniya Private University
Khulod Mohammed Al Wataniya Private University
Zabia Khallouf Al Wataniya Private University

DOI:

https://doi.org/10.5281/zenodo.21788863

Keywords:

Molecular Modeling, Black Fungus, Natural Compounds, 14-alpha Demethylase

Abstract

Objective: A study for the design of a library of natural compounds aimed at theoretically investigating their effect on the 14-alpha demethylase enzyme for the treatment of mucosal fungal disease using molecular modeling techniques.

Materials and Methods: A virtual screening study was conducted on a set of natural compounds representing various chemical classes found in plants. A library of 188 compounds was constructed using the PubChem and ZINC databases, and the compounds were downloaded in mol2 format to ensure compatibility with molecular modelling software. The target enzyme, 14-alpha demethylase, was retrieved from the Protein Data Bank (PDB) under the code 5FSA, with the co-crystallized ligand Posaconazole (code X2N). Computational analysis was carried out using iGEMDOCK to screen the compound library and identify the most promising natural inhibitors. Further, precise molecular modelling and docking studies were performed using ArgusLab to analyse interactions at the binding site in detail.

Results: The virtual screening revealed that the binding energies of the natural compounds ranged from -155.97 KJ/mol for Betanidin to -50.56 KJ/mol for Pinen. Notably, 12 compounds exhibited stronger binding affinities than the reference drug Posaconazole, which had a binding energy of -135.25 KJ/mol. Detailed molecular docking using ArgusLab confirmed these interactions and provided three-dimensional visualizations of the ligand-enzyme complexes.

Conclusion: This theoretical study highlights the potential of reintroducing natural compounds for the treatment of fungal infections, particularly mucormycosis. The selected natural compounds demonstrated significant inhibitory activity against the 14-alpha demethylase enzyme and may be used synergistically with synthetic antifungals to enhance therapeutic efficacy and broaden the spectrum of antifungal action.

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