Analysis of the Glutamate Agonist LY404,039 Binding to Nonstatic Dopamine Receptor D2 Dimer Structures and Consensus Docking
| Autor: | Serdar Durdagi, Matthias Stein, Busecan Aksoydan, Philip Seeman, Ramin Ekhteiari Salmas, Mine Yurtsever, Isik Kantarcioglu, Ismail Erol |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist Molecular model Physiology Guanine medicine.drug_class Stereochemistry Cognitive Neuroscience Dimer Molecular Dynamics Simulation Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dopamine receptor D2 medicine chemistry.chemical_classification Receptors Dopamine D2 Cell Biology General Medicine Bridged Bicyclo Compounds Heterocyclic Ligand (biochemistry) Cyclic S-Oxides Amino acid Molecular Docking Simulation 030104 developmental biology chemistry Docking (molecular) Dopamine Agonists 030217 neurology & neurosurgery |
| Zdroj: | ACS Chemical Neuroscience |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.7b00070 |
| Popis: | Dopamine receptor D2 (D2R) plays an important role in the human central nervous system and is a focal target of antipsychotic agents. The D2HighR and D2LowR dimeric models previously developed by our group are used to investigate the prediction of binding affinity of the LY404,039 ligand and its binding mechanism within the catalytic domain. The computational data obtained using molecular dynamics simulations fit well with the experimental results. The calculated binding affinities of LY404,039 using MM/PBSA for the D2HighR and D2LowR targets were −12.04 and −9.11 kcal/mol, respectively. The experimental results suggest that LY404,039 binds to D2HighR and D2LowR with binding affinities (Ki) of 8.2 and 1640 nM, respectively. The high binding affinity of LY404,039 in terms of binding to [3H]domperidone was inhibited by the presence of a guanine nucleotide, indicating an agonist action of the drug at D2HighR. The interaction analysis demonstrated that while Asp114 was among the most critical amino acids for ... |
| Databáze: | OpenAIRE |
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