Virtual Screening of Natural compounds for the Identification of Putative Lead Molecules for the Inhibition of Dopamine Receptor.

Abstract

Dopamine controls locomotion, neuroendocrine secretion, and cognition. Various physiological processes of dopamine are regulated by a combination of five other G proteins through the receptor subtypes i.e., D1 D2 D3 D4 and D5. Dopamine receptor mechanisms involving Dopamine1 and Dopamine2 receptors are predominant in intervening anxiety. In several brain disorders like occurrence of Parkinson’s Disease, dopamine neurotransmission is involved. Dopamine receptor antagonists are clinically significant, but these medications have different reactions, connected to their activity on the dopamine. Many medications being used in this treatment possess adverse effects. Different compounds found in plants makes them an elective source for new lead compounds for different targets. Herbal plants comprising inhibitors can be utilized as lead molecules to manufacture potent medications. Here, in this study we have investigated different natural compounds of plants origin that can act as natural inhibitors of dopamine D2 receptor. These compounds were docked with DRD2 receptor whose docking scores predicted that they are stronger inhibitors having covalent bonding, hydrogen bonding and ionic bonding interaction, as compared to already FDA approved drugs against this receptor. The docking score shown by natural inhibitors was -13.65 whereas docking score of synthetic drugs was -9.95. Moreover, fragment-based docking of natural inhibitors predict that they are strong inhibitors of dopamine with docking scores of -12.10. We designed new inhibitors that show maximum protein ligand interactions with better docking scores. We propose that natural compounds and newly designed compounds from natural origin can be used to inhibit the reuptake of dopamine in several neurological diseases. The outcome of the current project can be further extended through experimental validation of identified hits.