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Research Paper|Volume 13, Issue 12|pp 16620—16636

Computational study on new natural compound agonists of dopamine receptor

Hui Li1, Wenzhuo Yang3, Jianxin Xi3, Zhenhua Wang3, Han Lu3, Zhishan Du3, Weihang Li4, Bo Wu5, Shanshan Jiang7, Yida Peng6, Jingyi liu8, Luwei liu8, Xiangheng Zhang2, Jiachun Feng1
  • 1Department of Neurology, The First Hospital of Jilin University, Changchun, China
  • 2Department of Neurosurgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
  • 3Clinical College, Jilin University, Changchun, China
  • 4Department of Orthopaedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
  • 5Department of Orthopaedic Surgery, The First Hospital of Jilin University, Changchun, China
  • 6College of Computer Science and Technology, Jilin University, Changchun, China
  • 7Chinese Academy of Sciences, Research Group of Evolution and Population Genomics, Institute of Zoology, Beijing, China
  • 8Department of Biomedical Informatics, Harvard Medical School, Cambridge, MA 02115, USA
* Equal contribution
Received: September 21, 2020Accepted: April 29, 2021Published: June 25, 2021
https://doi.org/10.18632/aging.203180

Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting dopamine receptors, Dopamine receptor agonists are a class of drugs similar in function and structure to dopamine and can directly act on dopamine receptors and activate it. Clinically, Dopamine receptor agonist drugs have achieved significant therapeutic effects on prolactinoma and Parkinson's Disease.

In the study, we virtually screened a series of potential effective agonists of Dopamine receptor by computer techniques. Firstly, we used the Molecular Docking (LibDock) step to screen out some molecules that can dock well with the protein. Then, analysis of toxicity prediction and ADME (adsorption, distribution, metabolism and excretion) were carried out. More precise molecular docking (CDOCKER) and 3-Dimensional Quantitative Structure-Activity Relationship Modeling Study(3D-QSAR) pharmacophore generation were implemented to research and explore these compounds' binding mechanism with Dopamine receptor. Last but not least, to assess compound's binding stabilities, we carried out a molecular dynamic analysis. As the results show, two compounds (ZINC000008860530 and ZINC000004096987) from the small molecule database (ZINC database) were potential effective agonists of Dopamine receptor. These two compounds can combine with Dopamine receptor with higher affinity and proved to be no toxic. The cell experiment showed that two compounds could inhibit the proliferation and PRL secretion of MMQ cells (pituitary tumor cells). Thus, this study provided valuable information about Dopamine receptor agonist-based drug discovery. So, this study will benefit patients with prolactinoma and Parkinson’s disease a lot.