Flexible molecular docking simulation of peptide compounds as inhibitor of GluI host protein for dengue fever therapy

• Main Authors: Stephanie, Filia, Alkaff, Ahmad Husein, Tambunan, Usman Sumo Friend
• Format: Conference Proceeding
• Language: English
• Subjects: Binding energy; Dengue fever; Glucosidase; Inhibitors; Life cycle analysis; Molecular docking; Molecular structure; Peptides; Proteins; Screening; Simulation; Viral diseases; Viruses
• ISSN: 0094-243X; 1551-7616
• DOI: 10.1063/5.0005237

Dengue fever is one of the most prevalent diseases, which caused by dengue virus (DENV). Drug development against DENV is difficult due to the high variance among the four DENV serotypes. Targeting host protein alpha-glucosidase (GluI), which responsible for one particular step of the DENV life cycle, is an alternative approach to overcome the DENV variance problem. In this study, the peptide that can act as an inhibitor towards GluI was screened through several in silico process and underwent molecular docking simulation with the 3D structure of GluI. The peptide was chosen as the ligands as they possess great diversity and bioactivity. The target protein with PDB ID: 4J5T was chosen to represent the human GluI, and 55,467 peptide compounds were retrieved from PubChem database. The peptide compounds underwent virtual screening using Osiris DataWarrior 4.2.1 and MOE 2014.09 to search for a peptide with a suitable feature as GluI inhibitor. After the virtual screening, about 1,792 peptide compounds were subjected to three steps of molecular docking simulations, namely virtual screening, rigid docking, and flexible docking simulation to identify the most potent inhibitor. Argimicin A, Zwittermicin A, and Rapastinel are three best peptides inhibitor candidate against GluI as they showed better affinity with Gibbs free binding energy of -11.7890, -8.7730, and -8.1342 Kcal/mol, respectively, than the standard drugs, Castanospermine and Deoxynojirimycin with the respective Gibbs free binding energy of -6.9275 and -6.3320. The ADME-Tox properties and drug-likeness of these candidates were compared to the standards, and the result showed that the candidates have a suitable pharmacological properties to be used for dengue infection therapy.