Structure-based virtual screening of hypothetical inhibitors of the enzyme longiborneal synthase - a potential target to reduce Fusarium head blight disease

A - Papers appearing in refereed journals

Bresso, E., Leroux, V., Urban, M., Hammond-Kosack, K. E., Maigret, B. and Martins, N. F. 2016. Structure-based virtual screening of hypothetical inhibitors of the enzyme longiborneal synthase - a potential target to reduce Fusarium head blight disease. Journal Of Molecular Modeling. 22, p. 163.

AuthorsBresso, E., Leroux, V., Urban, M., Hammond-Kosack, K. E., Maigret, B. and Martins, N. F.
Abstract

Fusarium head blight (FHB) is one of the most destructive diseases of wheat and other cereals worldwide. During infection, the Fusarium fungi produce mycotoxins that represent a high risk to human and animal health. Developing small-molecule inhibitors to specifically reduce mycotoxin levels would be highly beneficial since current treatments unspecifically target the Fusarium pathogen. Culmorin possesses a well-known important synergistically virulence role among mycotoxins, and longiborneol synthase appears to be a key enzyme for its synthesis, thus making longiborneol synthase a particularly interesting target. This study aims to discover potent and less toxic agrochemicals against FHB. These compounds would hamper culmorin synthesis by inhibiting longiborneol synthase. In order to select starting molecules for further investigation, we have conducted a structure-based virtual screening investigation. A longiborneol synthase structural model is first built using homology modeling, followed by molecular dynamics simulations that provided the required input for a protein–ligand ensemble docking procedure. From this strategy, the three most interesting compounds (hits) were selected among the 25 top-ranked docked compounds from a library of 15,000 drug-like compounds. These putative inhibitors of longiborneol synthase provide a sound starting point for further studies involving molecular modeling coupled to biochemical experiments. This process could eventually lead to the development of novel approaches to reduce mycotoxin contamination in harvested grain.

Year of Publication2016
JournalJournal Of Molecular Modeling
Journal citation22, p. 163
Digital Object Identifier (DOI)doi:10.1007/s00894-016-3021-1
Open accessPublished as bronze (free) open access
FunderBiotechnology and Biological Sciences Research Council
Funder project or codeWheat
Pathogen-Host Interactions Database: PHI Database [2012-2017]
[20:20 Wheat] Protecting yield potential of wheat
PhytoPath, an infrastructure for hundreds of plant pathogen genomes [2014-2017]
Publisher's version
Copyright license
Publisher copyright
Output statusPublished
Publication dates
Online21 Jun 2016
Publication process dates
Accepted27 May 2016
Copyright licensePublisher copyright
PublisherSpringer
ISSN1610-2940

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