Prisil Naveentha, X and Brindha Durairaj, E (2024) Hybrid virtual screening and molecular dynamics approach for identification of allosteric modulator of EAAT2. Hybrid virtual screening and molecular dynamics approach for identification of allosteric modulator of EAAT2.

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Abstract

EAAT2, a glial protein that clears excess glutamate from synapses, regulates synaptic transmission, and prevents
excitotoxicity in neurons is impaired by Aβ induced oxidative stress in neurodegenerative diseases like Alz�heimer’s disease. Therefore, compounds that enhance EAAT2 function by reducing oxidative stress and excito�toxicity might be neuroprotective. The current study aimed to identify allosteric activators targeting EAAT2 in
the treatment of AD using in-silico. Virtual screening identified promising candidates from the specs database and
demonstrated excellent binding affinity with the allosteric pocket of EAAT2. ADMET studies determined the
lipophilicity of the compounds and displayed good permeability across the BBB. MM-GBSA analysis further
showed higher binding free energy for two compounds. Subsequently, molecular dynamics simulations
confirmed the stability of the complex and its binding ability to the allosteric pocket of EAAT2. These findings
identified the compound AK-968/15360623 as a promising lead molecule that could enhance EAAT2 function
and prevent neurodegeneration in AD

Item Type: Article
Uncontrolled Keywords: EAAT2 AK-968/15360623 Virtual screening Molecular dynamics Alzheimer’s disease
Divisions: PSG College of Arts and Science > Department of Chemistry
Depositing User: Mr Team Mosys
Date Deposited: 23 Sep 2024 09:24
Last Modified: 23 Sep 2024 09:24
URI: https://ir.psgcas.ac.in/id/eprint/2275

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