Work

Exploring Ligand–Receptor Dynamics: Comparative Analysis of Catecholamines, L‐DOPA, and Epinine Binding to the D 2 Dopamine Receptor

Year: 2025

Type: article

Abstract: ABSTRACT The receptor–ligand interactions are crucial for understanding the mechanisms of biological regulation and these interactions give a theoretical basis for the design and discovery of new drug targets. Understanding the molecular interactions between D 2 dopamine receptor and dopamine‐related analogues is essential for designing effective therapeutics. In this study, we performed a comprehensive computational investigation of the binding interactions between D 2 R and a set of catecholamines (dopamine, adrenaline, and noradrenaline) along with L‐DOPA and epinine, structurally related analogues with pharmacological significance. Molecular docking was carried out to predict binding poses and affinities, followed by molecular dynamics (MD) simulations to assess the stability and conformational dynamics of the ligand‐receptor complexes. Binding free energy using the MM‐PBSA method, NCIPLOT, QTAIM and SAPT energy decomposition are carried out to provide quantitative insights into ligand binding strengths. The results indicated that L‐DOPA exhibits the most stable interaction with D 2 R, forming persistent hydrogen bonds and hydrophobic contacts within the receptor's orthosteric binding site.

Source: Advanced Theory and Simulations

DOI: 10.1002/adts.202501486

Authors: Bhabesh Baro, Biplab Sarkar

Institution: North Eastern Hill University

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

Open Access status: bronze

Funders: North-Eastern Hill University, Department of Science and Technology, Ministry of Science and Technology, India, University Grants Commission, Science and Engineering Research Board

Awards: G6514320455, G7370161994, G90293465