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Updated: Jan 17, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Exploring molecular structural requirement for AChE inhibition through multi-chemometric and dynamics simulation
Tabassum Hossain1, Achintya Saha1, Arup Mukherjee1
1a Department of Chemical Technology , University of Calcutta , 92, A. P. C. Road, Kolkata , 700009 , India.
Abstract:
The acetylcholinesterase enzyme (AChE) plays an important role in central and peripheral nervous systems. Acetylcholine (ACh) acts through the regulation of AChE activity, which can play a key role in accelerating senile amyloid β-peptide (Aβ) plaque deposition. Therefore, inhibition of the AChE enzyme can be used as a key principle to prevent ACh depletion. The present study has been emphasized to explore both ligand- and structure-based 3D QSAR, HQSAR, pharmacophore, molecular docking and simulation studies on a set of structurally diverse inhibitors to optimize prime structural features responsible for selective binding to AChE, and vis-à-vis inhibiting enzyme activity. The pharmacophore model showed the importance of HB acceptor and donor, positive ionization and hydrophobic features of the molecule for effective binding. Structure-based docking and simulation studies adjudged the significance of features obtained from ligand-based 3D QSAR, CoMFA (Q2 = .608, [Formula: see text] = .700), CoMSIA (Q2 = .632, [Formula: see text] = .734), HQSAR (Q2 = .850, [Formula: see text] = .693) and pharmacophore (Q2 = .839, ROCscore = .769) models. The aim of the present study is to identify the essential structural and physicochemical profiles of molecules that can provide therapeutic benefits with less toxicity. Structurally diverse compounds have been used for the study, and the generated models showed the large applicability domain.
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