Molecular modeling studies for exploring structural requirement of acetylcholinesterase inhibitors

ACHINTYA, SAHA and TABASSUM, HOSSAIN (2016) Molecular modeling studies for exploring structural requirement of acetylcholinesterase inhibitors. In: Fourth International Conference on Advances in Bio-Informatics and Environmental Engineering - ICABEE 2016, 18-19 August 2016, Rome, Italy.

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Abstract

Inhibition of the neurotransmitter acetylcholine (ACh) can control the alzheimer’s disease (AD). The ACh hydrolyzes to produce choline and acetyl groups through acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the synaptic region, which play a key role in accelerating senile amyloid β-peptide (Aβ) plaque depositions, leads to generation of AD. The present study has been emphasized to explore both ligand- and structure-based QSAR and docking studies on a set of structurally diverse compounds to explore prime structural features responsible for selective binding to AChE, vis–a-vis inhibiting enzyme activity. Both the studies showed the importance of HB acceptor and donor, and hydrophobic features of the molecule for effective binding. Systematic comparisons revealed that structure-based study has advantages in efficiently identifying potent hits with structural diversity over simple ligand-based study. Structure-based QSAR study (site score = 1.006) adjudged the significance of features obtained from ligand-based QSAR model (ROC score = 0.850, sensitivity = 0.710, specificity = 0.932). Presence of electronegative groups, and acyclic and aromatic rings in the molecular scaffold depict the importance in selective AChE inhibition.

Item Type: Conference or Workshop Item (Paper)
Uncontrolled Keywords: AChE, Bayesian model, docking, Site Map analysis
Depositing User: Mr. John Steve
Date Deposited: 22 Mar 2019 10:25
Last Modified: 22 Mar 2019 10:25
URI: http://publications.theired.org/id/eprint/785

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