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

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...

Full description

Saved in:
Bibliographic Details
Published inChemistry Africa Vol. 7; no. 2; pp. 1151 - 1164
Main Authors Rathod, Sanket, Bhande, Diksha, Pawar, Swaranjali, Gumphalwad, Kondba, Choudhari, Prafulla, More, Harinath
Format Journal Article
LanguageEnglish
Published Cham Springer International Publishing 01.03.2024
Subjects
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
Inorganic Chemistry
Organometallic Chemistry
Short Communication
DFT study
Antifungal
Rpd3
Molecular dynamics simulation
Lysine deacetylase
Molecular docking
Online AccessGet full text

Cover

More Information
Summary: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. Graphical Abstract
ISSN:2522-5758
2522-5766
DOI:10.1007/s42250-023-00766-5