biostudies-literatureUnknown2025Imran MThe increasing burden of schistosomiasis, compounded by the restriction imposed by monotherapeutic regimens, highlights the pressing need for new molecules that target specific molecular pathways. <i>Schistosoma mansoni</i> 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-Journal of tropical medicine1172449https://www.ebi.ac.uk/biostudies/studies/S-EPMC12721395biostudies-literatureQuantum-Mechanically Refined, Dynamics-Coupled, and AI-Augmented Elucidation of Epigenetic Inhibition: An In Silico Paradigm Targeting HDAC8 of &lt;i&gt;Schistosoma mansoni&lt;/i&gt;.PMC12721395Alrehaili AAImran MMbunge ERehman ZUDzinamarira TAlhuthali HMAlzahrani ARJawaid TfalseQuantum-Mechanically Refined, Dynamics-Coupled, and AI-Augmented Elucidation of Epigenetic Inhibition: An In Silico Paradigm Targeting HDAC8 of &lt;i&gt;Schistosoma mansoni&lt;/i&gt;.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. <i>Schistosoma mansoni</i> 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-2025-01-01T00:00:00Z20252026-06-08T05:31:43.02Z2026-06-08T03:08:54.445ZS-EPMC127213954143862210.1155/jotm/1172449