Identification of small molecule activators for ErbB 4 receptor to enhance oligodendrocyte regeneration by in silico approach

ErbB receptors are involved in regulation of proliferation, differentiation and migration of oligodendrocytes. Oligodendrocytes are myelin producing cells of CNS which ensheaths multiple axons. Regeneration of oligodendrocytes in CNS fails due to its poor regenerative potential. ErbB 4 is involved in regeneration both during adult and developmental stage via NRG 1 mediated regenerative signaling. Hence, we attempted to identify activator molecules of ErbB 4 receptor to improve this regenerative process in CNS. In current investigation, pharmacophore modeling via molecular docking and pharmacokinetics study were used to identify lead compounds for ErbB 4 activators. Selected phytochemicals were docked on tyrosine kinase domain and extracellular domain of ErbB 4 by using Autodock vina and their binding energies were analyzed. Those phytochemicals which were successfully docked on tyrosine kinase domain were subjected to in silico pharmacokinetics study by using molinspiration and swissADME. Lead compounds were identified for pharmacophore generation using 'pharmagist'. Pharmacophore models were composed of two hydrogen bond donor, one hydrogen bond acceptor and one hydrophobic feature. Here, we report that pharmacophore generated by using Ginkgolide A, Hesperetin, Naringenin, Pelargonidin and Melatonin may serve as a good compound to develop activator of ErbB 4 receptor.