Neuroglobin activator In Silico found from Mirabilis Jalapa for stroke treatment

• Main Authors: Pangestu, Adika Putra, Indarto, Dono, Balgis
• Format: Conference Proceeding
• Language: English
• Subjects: Binding sites; Bioinformatics; Hypoxia; Molecular conformation; Molecular docking; Phytochemicals; Plants (botany); Proteins
• ISSN: 0094-243X; 1551-7616
• DOI: 10.1063/1.5062800

Stroke is among the leading causes of death around the globe, including in Indonesia, and recombinant tissue plasminogen activator (rtPA) is a recommended treatment for this disease. This drug is only effective, however, when administered early after stroke diagnosis and has some adverse effects. Neuroglobin (Ngb) is a neuroprotective protein and is activated by the 14-3-3 protein. During hypoxia, the 14-3-3 protein migrates into neuron nuclei resulting in reduced Ngb activation. Replacement of the 14-3-3 protein could be a potential avenue to explore for developing a new stroke treatment drug. Identification of phytochemicals through virtual screening are also a promising prospect for treating stroke. The purpose of this study was therefore to find an Ngb activator derived from Indonesian herbal plants in silico. This bioinformatics research study use the molecular docking approach; the 457 Indonesian phytochemicals in the HerbalDB that met Lipinski’s criteria were used as research samples, with the 14-3-3 protein as a standard compound. Because Ngb and 14-3-3 protein are both large molecules (> 17 kDa), these proteins had to be cut into smaller sizes to fit and validate in the AutoDock Vina 1.1.2 software. Interaction between selected phytochemicals and Ngb was analyzed using AutoDock Vina 1.1.2 and Pymol 2.0.6 was used to visualize docking results. The phytochemical-generated Ngb activator was determined according to docking scores, binding sites, and molecular conformation. Two truncated 14-3-3 proteins bound to truncated Ngb with -3,7 and -5,1 kkal/mol docking scores and binding sites at Ser17 and Ser50 residues, respectively. There were two phytochemicals (Miraxanthin-III and Strigol) that had lower docking scores compared with the standard compound. In addition, Miraxanthin-III was superior to 14-3-3 protein as an Ngb activator due to lower docking scores, similar binding sites, and conformation. This phytochemical was a secondary metabolite found in Mirabilis Jalapa. In conclusion, Miraxanthin-III and Strigol could interact with Ngb, but Miraxanthin-III appears to be the potential Ngb activator in silico.