Locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors

Neuraminidase (NA) of influenza is a key target for virus infection control and the recently discovered open 150-cavity in group-1 NA provides new opportunity for novel inhibitors design. In this study, we used a combination of theoretical methods including fragment docking, molecular linking and mo...

Full description

Saved in:
Bibliographic Details
Main Authors: Han, Nanyu, Mu, Yuguang
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2013
Subjects:
Online Access:https://hdl.handle.net/10356/103809
http://hdl.handle.net/10220/16533
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-103809
record_format dspace
spelling sg-ntu-dr.10356-1038092023-02-28T17:03:36Z Locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors Han, Nanyu Mu, Yuguang School of Biological Sciences DRNTU::Science::Biological sciences::Microbiology Neuraminidase (NA) of influenza is a key target for virus infection control and the recently discovered open 150-cavity in group-1 NA provides new opportunity for novel inhibitors design. In this study, we used a combination of theoretical methods including fragment docking, molecular linking and molecular dynamics simulations to design ligands that specifically target at the 150-cavity. Through in silico screening of a fragment compound library on the open 150-cavity of NA, a few best scored fragment compounds were selected to link with Zanamivir, one NA-targeting drug. The resultant new ligands may bind both the active site and the 150-cavity of NA simultaneously. Extensive molecular dynamics simulations in explicit solvent were applied to validate the binding between NA and the designed ligands. Moreover, two control systems, a positive control using Zanamivir and a negative control using a low-affinity ligand 3-(p-tolyl) allyl-Neu5Ac2en (ETT, abbreviation reported in the PDB) found in a recent experimental work, were employed to calibrate the simulation method. During the simulations, ETT was observed to detach from NA, on the contrary, both Zanamivir and our designed ligand bind NA firmly. Our study provides a prospective way to design novel inhibitors for controlling the spread of influenza virus. Published version 2013-10-16T07:53:56Z 2019-12-06T21:20:46Z 2013-10-16T07:53:56Z 2019-12-06T21:20:46Z 2013 2013 Journal Article Han, N., & Mu, Y. (2013). Locking the 150-Cavity Open: In Silico Design and Verification of Influenza Neuraminidase Inhibitors. PLoS ONE, 8(8). 1932-6203 https://hdl.handle.net/10356/103809 http://hdl.handle.net/10220/16533 10.1371/journal.pone.0073344 24015302 en PLoS ONE © 2013 Han et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences::Microbiology
spellingShingle DRNTU::Science::Biological sciences::Microbiology
Han, Nanyu
Mu, Yuguang
Locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors
description Neuraminidase (NA) of influenza is a key target for virus infection control and the recently discovered open 150-cavity in group-1 NA provides new opportunity for novel inhibitors design. In this study, we used a combination of theoretical methods including fragment docking, molecular linking and molecular dynamics simulations to design ligands that specifically target at the 150-cavity. Through in silico screening of a fragment compound library on the open 150-cavity of NA, a few best scored fragment compounds were selected to link with Zanamivir, one NA-targeting drug. The resultant new ligands may bind both the active site and the 150-cavity of NA simultaneously. Extensive molecular dynamics simulations in explicit solvent were applied to validate the binding between NA and the designed ligands. Moreover, two control systems, a positive control using Zanamivir and a negative control using a low-affinity ligand 3-(p-tolyl) allyl-Neu5Ac2en (ETT, abbreviation reported in the PDB) found in a recent experimental work, were employed to calibrate the simulation method. During the simulations, ETT was observed to detach from NA, on the contrary, both Zanamivir and our designed ligand bind NA firmly. Our study provides a prospective way to design novel inhibitors for controlling the spread of influenza virus.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Han, Nanyu
Mu, Yuguang
format Article
author Han, Nanyu
Mu, Yuguang
author_sort Han, Nanyu
title Locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors
title_short Locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors
title_full Locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors
title_fullStr Locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors
title_full_unstemmed Locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors
title_sort locking the 150-cavity open : in silico design and verification of influenza neuraminidase inhibitors
publishDate 2013
url https://hdl.handle.net/10356/103809
http://hdl.handle.net/10220/16533
_version_ 1759855921765285888