What question did this study set out to answer?

This study aims to elucidate the mechanisms of action for selected HDAC8 inhibitors through computational methods.

May 14, 2026Ankara Universitesi Eczacilik Fakultesi Dergisi0 citationsOpen Access

Investigation of the Inhibition Mechanism of Some Hdac8 Inhibitors Through Computational Methods

MMMuhammed Tılahun MuhammedSüleyman Demirel University İSİrem SarıSuleyman Demirel University SŞSude Nur ŞahanSuleyman Demirel University

Key Points

This study aims to elucidate the mechanisms of action for selected HDAC8 inhibitors through computational methods.
Binding modes of HDAC8 inhibitors were explored via LibDock docking.
Molecular dynamics simulation was conducted using GROMACS 2024 for HDAC8-inhibitor complexes.
The study analyzed critical residues such as His180 and Tyr306 during binding.
Compound d showed the highest binding potential to HDAC8, confirming its effectiveness.
Hydroxamic acid, amide groups, and aromatic rings play significant roles in HDAC8 inhibition.
MD simulations revealed that HDAC8-inhibitor complexes remained stable over 200 ns.

Abstract

Objective: Cancer remains one of the leading causes of death around the globe. Current treatment methods are known for their side effects and resistance development. Therefore, there is a growing need for novel therapeutic strategies that are more effective with lower toxicity. Histone deacetylase 8 (HDAC8) overexpression has been linked to poor prognosis in cancer. Hence, HDAC8 is an attractive target in developing new anticancer agents. The objective of this study has been to elucidate mechanisms of action for some selected HDAC8 inhibitors through computational methods.Material and Method: In this study, binding modes of selected HDAC8 inhibitors to the enzyme structure were explored through docking via LibDock and molecular dynamics (MD) simulation via GROMACS 2024.Result and Discussion: The docking study disclosed that compound d exhibited the highest binding potential to the HDAC8 structure. The roles of hydroxamic acid, amide group, and aromatic rings in the HDAC8 inhibition were affirmed by the docking study. His180 and Tyr306 residues were found to be critical residues in the binding. The MD simulation study disclosed that HDAC8-inhibitor complexes procured from the docking were stable during the 200 ns simulation.

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