Issue 12, 2025

Molecular mechanism behind the cholinium-taurate ionic liquid in stabilisation of HDAC2 for alcohol use disorders: insights from DFT and MD simulations

Abstract

This study explores how an active pharmaceutical ingredient-ionic liquid (API-IL), cholinium taurate ([Cho]+[Tau]) IL, may alter the structural and functional stability of histone deacetylase 2 (HDAC2), which is a crucial enzyme linked to alcohol use disorder (AUD). A particular hallmark of AUD, which is a worldwide health burden, is epigenetic dysregulation, in which HDAC2 plays a significant role in gene silencing and chronic neuroplastic alterations. Leveraging the unique physicochemical properties of [Cho]+[Tau]IL, including hydrogen bond (H-bond) formation and structural reinforcement, we explored its therapeutic potential through comprehensive computational approaches. Density functional theory (DFT) analyses provided insights into the hydration and stability profiles of [Cho]+[Tau]IL, while 200 ns molecular dynamics (MD) simulations elucidated its interaction with HDAC2 at the molecular level. Strikingly, the [Tau] ion emerged as a key modulator of HDAC2 stability, facilitating conformational transitions in the enzyme's secondary structure, notably from turns to helices. This stabilisation was mediated by intricate hydration networks, water-mediated H-bonds, and diverse non-covalent interactions (NCIs). The rigorous nature of our structural analyses confirmed the potential of [Cho]+[Tau]IL as a robust stabiliser of HDAC2, offering a novel therapeutic avenue for AUD treatment. This work underscores the promise of API-ILs in targeting epigenetic regulators and advancing strategies for AUD, providing a solid foundation for future research in this area.

Graphical abstract: Molecular mechanism behind the cholinium-taurate ionic liquid in stabilisation of HDAC2 for alcohol use disorders: insights from DFT and MD simulations

Supplementary files

Article information

Article type
Paper
Submitted
29 Huk 2024
Accepted
24 Yan 2025
First published
24 Yan 2025

Phys. Chem. Chem. Phys., 2025,27, 6263-6277

Molecular mechanism behind the cholinium-taurate ionic liquid in stabilisation of HDAC2 for alcohol use disorders: insights from DFT and MD simulations

S. M. E. Rubavathy, G. Hema and M. Prakash, Phys. Chem. Chem. Phys., 2025, 27, 6263 DOI: 10.1039/D4CP04535A

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