The Pivotal Distinction between Antagonists' and Agonists' Binding into Dopamine D4 Receptor-MD and FMO/PIEDA Studies.

ABSTRACT: The dopamine D4 receptor (D4R) is a promising therapeutic target in widespread diseases, and the search for novel agonists and antagonists appears to be clinically relevant. The mechanism of binding to the receptor (R) for antagonists and agonists varies. In the present study, we conducted an in-depth computational study, teasing out key similarities and differences in binding modes, complex dynamics, and binding energies for D4R agonists and antagonists. The dynamic network method was applied to investigate the communication paths between the ligand (L) and G-protein binding site (GBS) of human D4R. Finally, the fragment molecular orbitals with pair interaction energy decomposition analysis (FMO/PIEDA) scheme was used to estimate the binding energies of L-R complexes. We found that a stro

SUBMITTER: Sliwa P 

PROVIDER: S-EPMC10815553 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature