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Identification of Potential Hits against Fungal Lysine Deacetylase Rpd3 via Molecular Docking, Molecular Dynamics Simulation, DFT, In-Silico ADMET and Drug-Likeness Assessment

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Abstract

Fungal histone deacetylases (HDACs) are enzymes known for their crucial role in gene expression regulation through histone deacetylation, leading to chromatin compaction and transcriptional control. Among them, Rpd3, a lysine deacetylase, has been extensively studied for its involvement in chromatin remodeling, gene expression, and various biological processes such as development, cell cycle progression, and stress response. Rpd3's significance in fungal pathogenesis makes it a potential target for antifungal therapies. This study utilized advanced computational tools to identify biogenic molecule hits against a homology-modeled Rpd3 structure. Molecular dynamics simulations verified the stability of the hits while docking studies revealed strong binding affinities (< – 8 kcal/mol) for Rpd3-ZINC000019941755, Rpd3-ZINC000005854718, and Rpd3-ZINC000014762752 complexes. The correlation between binding interactions and HOMO–LUMO properties was established through density functional theory calculations. Additionally, in silico pharmacokinetic and drug-likeness assessments highlighted the potential of these hits as drug candidates. Consequently, ZINC000019941755, ZINC000005854718, and ZINC000014762752 emerge as promising candidates for further investigation.

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All the necessary data related to work are included in paper. The additional data availability statement is not applicable.

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  1. Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, MS, 416 013, India

    Sanket Rathod, Diksha Bhande, Swaranjali Pawar, Kondba Gumphalwad, Prafulla Choudhari & Harinath More

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Rathod, S., Bhande, D., Pawar, S. et al. Identification of Potential Hits against Fungal Lysine Deacetylase Rpd3 via Molecular Docking, Molecular Dynamics Simulation, DFT, In-Silico ADMET and Drug-Likeness Assessment. Chemistry Africa 7, 1151–1164 (2024). https://doi.org/10.1007/s42250-023-00766-5

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