In silico study of Hydrogen Peroxide (H2O2) binding effect to Extracellular Signal-Regulated Kinases (ERK)

Abstract

H₂O₂ can provide a physiological response by activating Mitogen activated protein kinase (MAPK) signaling components, it can phosphorylate and activate several regulatory proteins, which are closely related to gene expression, and growth promotion. H₂O₂ has neuroprotective abilities and potential to be a complementary therapy. It can be implemented in Parkinson Disease (PD) therapy, by activating Extracellular signal-regulated kinases (ERK/1/2/5) play central role in the control of endothel cell proliferation and activate apoptosis signal-regulating kinase 1 (ASK1), key modulators of the apoptosis cell or death balance. The main pathology of PD is amyloid fibrils composed of αSyn (α-Synuclein), can cause disruption of the blood-brain barrier (BBB.) Aggregate of αSyn caused mitochondrial dysfunction, dysregulation and apoptosis in barrier-type brain endothelial cells (BECs), it leads BBB leakage, increase BBB permeability and disrupt L-DOPA transport. Therefore, treatments that prevent vascular degeneration may be new targets for the of PD. This research used in silico method. The 3D structures of ligand and protein target was retrieved from PubChem and protein data bank (PDB). Ligand was converted using the Open Babel and molecular docking program used AutoDock Vina, as a plug-in in PyRx. Results were analysed using PyMOL and Discovery Studio. Molecular dynamics simulation used YASARA. From this study, H₂O₂ lowering RMSD and RMSF value of ERK 1/2/5 and ASK1. It is known that H₂O₂ can stabilize ERK 1/2/5 and ASK1.