Quantum-Mechanically Refined, Dynamics-Coupled, and AI-Augmented Elucidation of Epigenetic Inhibition: An In Silico Paradigm Targeting HDAC8 of <i>Schistosoma mansoni</i>.

ABSTRACT: The increasing burden of schistosomiasis, compounded by the restriction imposed by monotherapeutic regimens, highlights the pressing need for new molecules that target specific molecular pathways. Schistosoma mansoni histone deacetylase 8 (SmHDAC8), a zinc-dependent epigenetic regulator, has emerged as a nonredundant and druggable enzyme, critical for parasite survival, fertility, and chromatin homeostasis. In this study, we outline multiple-mode computational analysis involving structure-based virtual screening against a chemically diverse ligand library, frontier molecular orbital analysis through DFT, large-scale molecular dynamics (MD) simulations (500 ns), and molecular mechanics/gas-phase/Generalized Born (MM/GBSA) energy component analysis, complemented with machine learning-

SUBMITTER: Imran M 

PROVIDER: S-EPMC12721395 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature