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

Filia Stephanie, Ahmad Husein Alkaff, Usman Sumo Friend Tambunan

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

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.

Original languageEnglish
Title of host publication14th Joint Conference on Chemistry 2019
EditorsFitria Rahmawati, Teguh Endah Saraswati, Khoirina Dwi Nugrahaningtyas, Soerya Dewi Marliyana, Triana Kusumaningsih
PublisherAmerican Institute of Physics Inc.
ISBN (Electronic)9780735419964
DOIs
Publication statusPublished - 2 Jun 2020
Event14th Joint Conference on Chemistry 2019, JCC 2019 - Surakarta, Indonesia
Duration: 10 Sep 201911 Sep 2019

Publication series

NameAIP Conference Proceedings
Volume2237
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Conference

Conference14th Joint Conference on Chemistry 2019, JCC 2019
CountryIndonesia
CitySurakarta
Period10/09/1911/09/19

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