Format

Send to

Choose Destination
Appl Biochem Biotechnol. 2015 Oct;177(4):861-78. doi: 10.1007/s12010-015-1784-y. Epub 2015 Aug 25.

Receptor-Guided De Novo Design of Dengue Envelope Protein Inhibitors.

Author information

1
Department of Bioinformatics, Applied Botany Centre (ABC), Gujarat University, Ahmedabad, Gujarat, 380009, India.
2
Department of Botany, Gujarat University, Ahmedabad, Gujarat, 380009, India.
3
Department of Bioinformatics, Applied Botany Centre (ABC), Gujarat University, Ahmedabad, Gujarat, 380009, India. husolanki@yahoo.com.
4
Department of Botany, Gujarat University, Ahmedabad, Gujarat, 380009, India. husolanki@yahoo.com.

Abstract

Inhibitor design associated with the dynamics of dengue envelope protein at pre-fusion stage is a prominent strategy to interfere fusion transition of dengue virus with the host cell membrane. Receptor-guided de novo inhibitors were designed based on the knowledge of co-crystallized detergent, β-octyl glucoside. Pharmacophore features distribution showed the preference of aromatic groups with H bonding features connected to aliphatic bulky group as the skeleton for inhibitor design. Molecular dynamic simulations revealed (2R)-2-[(6-amino-1-oxohexan-2-yl)amino]-4-[6-(4-phenylpiperidine-1-yl)-1,2-benzoxazol-3-yl]butanoate as the probable binder which developed extensive conservative interactions despite the local pocket residues movements especially from kl β-hairpin, the key structural unit for initiating conformational changes required for fusion transition. The electronic and hydrophobic potentials also indicated that butanoate molecule as the initial lead for envelope protein inhibitors.

KEYWORDS:

De novo design; Dengue envelope; Docking; Dynamic simulations; Envelope inhibitors; Pharmacophore

PMID:
26299376
DOI:
10.1007/s12010-015-1784-y
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center