Computational Assessment of the Phytochemicals of Panax ginseng C.A. Meyer Against Dopamine Receptor D1 for Early Huntington's Disease Prophylactics.

A herb, Panax ginseng C.A. Meyer has been used traditionally for the treatment of various diseases. In this work, its chemical components have been explored by computational methods for the possibility of therapeutic potential against early Huntington's disease. The molecular docking calculations against dopamine receptor D1 (PDB ID: 7X2F) involved in pathogenesis of early Huntington's disease gave the binding affinities (kcal/mol) of schizandrin (-10.530), ergosterol (-10.124), protopanaxadiol (-9.650), panaxydol (-9.399), diphenhydramine (-9.358), and panasenoside (-9.358). The values for native ligand (-7.748) and some selected drugs, Nefazodone (-9.880), Risperidone (-9.752), and Haloperidol (-9.712) were higher revealing weaker interactions. The stability assessment of top protein-ligand adducts in terms of various geometrical and thermodynamical parameters extracted from 200 ns molecular dynamics simulations pointed to schizandrin, protopanaxadiol, and panasenoside as hit molecules. The minimal translational and rotational motion of the docked ligands at orthosteric pocket of the receptor at near physiological conditions hinted at the probability of it restricting or inhibiting over-activation of DRD1. The sustained thermodynamic spontaneity of complex formation reaction augmented the inferences derived from spatial results. The phytochemicals from Panax ginseng could be used in the prophylactics of early Huntington's disease and recommendation is made for further evaluation by experimental work.