INDONESIAN JOURNAL OF PHARMACY
Vol 26 No 1, 2015

CONSTRUCTION AND RETROSPECTIVE VALIDATION OF STRUCTURE-BASED VIRTUAL SCREENING PROTOCOLS TO IDENTIFY POTENT LIGANDS FOR HUMAN ADRENERGIC BETA-2 RECEPTOR

Istyastono, Enade Perdana (Division of Drug Discovery, Faculty of Pharmacy, Sanata Dharma University, Yogyakarta, Indonesia.)
Setyaningsih, Dewi (Division of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Sanata Dharma University, Yogyakarta, Indonesia)



Article Info

Publish Date
01 Jan 2015

Abstract

Adrenergic Beta-2 Receptor (ADRB2) is a member of G-protein coupled receptors family, which has served as targets for more than 30% of top-selling drugs in the market. Recently, an enhanced dataset of ligands and decoys for ADRB2 has publicly available. However, the original retrospective structure-based virtual screening campaign accompanying the dataset showed relatively poor quality with enrichment factor of true positives at 1% false positives (EF1%)value of 3.9. In this article, the construction and retrospective validation of a structure-based virtual screening protocol by employing PLANTS1.2 as the molecular docking software and PyPLIF as an alternative post docking scoring functions are presented. The results show that the developed protocols have better quality compared the original structure-based virtual screening with EF1% values of 24.24 and 8.22 by using ChemPLP from PLANTS1.2 and by using Tc-PLIF from PyPLIF, respectively. Further investigation by performing systematic filtering resulted in the identification of D113, S203, and N293 as molecular determinants in ADRB2-ligand binding.Key words: Structure-based virtual screening, molecular docking, adrenergic beta-2 receptor, protein-ligand interaction fingerprinting, molecular determinants

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Journal Info

Abbrev

3

Publisher

Subject

Medicine & Pharmacology

Description

Indonesian Journal of Pharmacy (ISSN-e: 2338-9486, ISSN-p: 2338-9427), formerly Majalah Farmasi Indonesia (ISSN: 0126-1037). The journal had been established in 1972, and online publication was begun in 2008. Since 2012, the journal has been published in English by Faculty of Pharmacy Universitas ...