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<p><i>Rhizopus delemar</i> 1,3-β-glucan synthase is a central enzyme in fungal cell wall biosynthesis and represents a critical target for antifungal intervention. Because its experimental structure is unavailable, we predicted the three-dimensional architecture of the enzyme using AlphaFold v2.2.0 and validated the model through structural superposition with the cryo-EM structure of <i>Saccharomyces cerevisiae</i> Fks1. The overall fold, including the regulatory, glycosyltransferase (GT) catalytic, and transmembrane domains, was conserved, supporting the reliability of the predicted model. Binding-site analysis, combined with structural alignment, confirmed that the primary druggable pocket lies within the GT catalytic groove. Virtual screening identified telmisartan as a promising inhibitor, which was further evaluated through a 100-ns molecular dynamics simulation. Stability metrics, principal component analysis, and free-energy landscape profiling indicated stable ligand accommodation, while MM/GBSA calculations revealed a favourable binding free energy of − 54.75&#xa0;kcal/mol. Together, these results establish a validated structural framework for <i>R. delemar</i> 1,3-β-glucan synthase and identify telmisartan as a compelling lead scaffold for future antifungal optimization.</p>

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Fungal Foe Unveiled: AlphaFold-based 3D structure prediction of Rhizopus delemar 1,3-β-Glucan synthase and virtual screening for the identification of potential inhibitors

  • 期刊论文

  • 发表日期：

    2026年2月17日

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  • Sandhya Kushwaha,
  • Deevena Kumari,
  • Sonia Kumari,
  • M. Elizabeth Sobhia

摘要

Rhizopus delemar 1,3-β-glucan synthase is a central enzyme in fungal cell wall biosynthesis and represents a critical target for antifungal intervention. Because its experimental structure is unavailable, we predicted the three-dimensional architecture of the enzyme using AlphaFold v2.2.0 and validated the model through structural superposition with the cryo-EM structure of Saccharomyces cerevisiae Fks1. The overall fold, including the regulatory, glycosyltransferase (GT) catalytic, and transmembrane domains, was conserved, supporting the reliability of the predicted model. Binding-site analysis, combined with structural alignment, confirmed that the primary druggable pocket lies within the GT catalytic groove. Virtual screening identified telmisartan as a promising inhibitor, which was further evaluated through a 100-ns molecular dynamics simulation. Stability metrics, principal component analysis, and free-energy landscape profiling indicated stable ligand accommodation, while MM/GBSA calculations revealed a favourable binding free energy of − 54.75 kcal/mol. Together, these results establish a validated structural framework for R. delemar 1,3-β-glucan synthase and identify telmisartan as a compelling lead scaffold for future antifungal optimization.