Structural Insights into Dopamine Receptor-Ligand Interactions: From Agonists to Antagonists. ACS Chem Neurosci 2024 Nov 20;15(22):4123-4131
Date
11/01/2024Pubmed ID
39485723DOI
10.1021/acschemneuro.4c00295Scopus ID
2-s2.0-85208389275 (requires institutional sign-in at Scopus site)Abstract
This study explores the intricacies of dopamine receptor-ligand interactions, focusing on the D1R and D5R subtypes. Using molecular modeling techniques, we investigated the binding of the pan-agonist rotigotine, revealing a universal binding mode at the orthosteric binding pocket. Additionally, we analyze the stability of antagonist-receptor complexes with SKF83566 and SCH23390. By examining the impact of specific mutations on ligand-receptor interactions through computational simulations and thermostability assays, we gain insights into binding stability. Our research also delves into the structural and energetic aspects of antagonist binding to D1R and D5R in their inactive states. These findings enhance our understanding of dopamine receptor pharmacology and hold promise for drug development in central nervous system disorders, opening doors to future research and innovation in this field.
Author List
Barbosa ED, Ma Y, Clift HE, Olson LJ, Zhu L, Liu WAuthor
Wei Liu PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepineBenzazepines
Binding Sites
Dopamine Agonists
Dopamine Antagonists
Humans
Ligands
Models, Molecular
Protein Binding
Receptors, Dopamine D1
Receptors, Dopamine D5
Tetrahydronaphthalenes
Thiophenes
