A computational workflow for membrane protein–ligand interaction studies: focus on α5-containing GABA (A) receptors

Sayed Mohamad, Syarifah Maisarah and Abd Halim, Khairul Bariyyah and Abdul Hamid, Azzmer Azzar and Che Has, Ahmad Tarmizi (2025) A computational workflow for membrane protein–ligand interaction studies: focus on α5-containing GABA (A) receptors. Bio-protocol, 15 (22). pp. 1-28. ISSN 23318325

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Abstract

In neuropharmacology and drug development, in silico methods have become increasingly vital, particularly for studying receptor–ligand interactions at the molecular level. Membrane proteins such as GABA (A) receptors play a central role in neuronal signaling and are key targets for therapeutic intervention. While experimental techniques like electrophysiology and radioligand binding provide valuable functional data, they often fall short in resolving the structural complexity of membrane proteins and can be time-consuming, costly, and inaccessible in many research settings. This study presents a comprehensive computational workflow for investigating membrane protein–ligand interactions, demonstrated using the GABA (A) receptor α5β2γ2 subtype and mitragynine, an alkaloid from Mitragyna speciosa (Kratom), as a case study. The protocol includes homology modeling of the receptor based on a high-resolution template, followed by structure optimization and validation. Ligand docking is then used to predict binding sites and affinities at known modulatory interfaces. Finally, molecular dynamics (MD) simulations assess the stability and conformational dynamics of receptor–ligand complexes over time. Overall, this workflow offers a robust, reproducible approach for structural analysis of membrane protein–ligand interactions, supporting early-stage drug discovery and mechanistic studies across diverse membrane protein targets.

Item Type:	Article (Journal)
Uncontrolled Keywords:	Membrane protein modeling, Molecular docking, Molecular dynamics simulation, Receptor–ligand interaction, GABA (A) receptor
Subjects:	Q Science > QR Microbiology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Science > Department of Biotechnology Kulliyyah of Science
Depositing User:	AP. Dr. Azzmer Azzar Abdul Hamid
Date Deposited:	16 Dec 2025 12:10
Last Modified:	16 Dec 2025 12:10
Queue Number:	2025-12-Q909
URI:	http://irep.iium.edu.my/id/eprint/125818

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