In silico study of Hydrogen Peroxide (H2O2) binding effect to Extracellular Signal-Regulated Kinases (ERK)
Athiyah Layla, Sri Widyarti, Sutiman Bambang Sumitro
Abstract
H2O2 can provide a physiological response by activating mitogen-activated potein kinase (MAPK) signaling components; it can phosphorylate and activate several regulatory proteinsclosely related togene expression and growth promotion. H2O2 has neuroprotective abilities and the potentialto be a complementary therapy. It can be implemented in Parkinson's Disease (PD) therapy by activating; Extracellular signal-regulated kinases (ERK/1/2/5), playing a central role in the control of endothelial cell proliferation, and triggering apoptosis signal-regulating kinase 1 (ASK1), critical modulators of the apoptosis cell or death balance. The primary pathology of PD is amyloid fibrils composed of αSyn (α-Synuclein). Aggregate of αSyn causes mitochondrial dysfunction, dysregulation, and apoptosis in brain endothelial cells (BECs); it leads to blood brain barrier (BBB) leakage and increases BBB permeability. Therefore, treatments that prevent vascular degeneration may be new targets for PD. This research used the in-silico method. The 3D ligand and protein target structures were retrieved from PubChem and the protein databank (PDB). Ligand was converted using the Open Babel, and the molecular docking program used AutoDock Vina as a plug-in in PyRx. Results were analyzed using PyMOL and Discovery Studio. Molecular dynamics simulation used YASARA. From this study, H2O2 lowered the RMSD and RMSF values of ERK 1/2/5 and ASK1. It is known that H2O2 stabilize ERK 1/2/5 and ASK1.
Article link: https://new.berkalahayati.org/index.php/jurnal/article/view/802/551