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. https://doi.org/10.1007/s00894-016-3021-1
Authors | Bresso, E., Leroux, V., Urban, M., Hammond-Kosack, K. E., Maigret, B. and Martins, N. F. |
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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 Publication | 2016 |
Journal | Journal Of Molecular Modeling |
Journal citation | 22, p. 163 |
Digital Object Identifier (DOI) | https://doi.org/10.1007/s00894-016-3021-1 |
Open access | Published as bronze (free) open access |
Funder | Biotechnology and Biological Sciences Research Council |
Funder project or code | Wheat |
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 | |
Publisher's version | Copyright license Publisher copyright |
Output status | Published |
Publication dates | |
Online | 21 Jun 2016 |
Publication process dates | |
Accepted | 27 May 2016 |
Copyright license | Publisher copyright |
Publisher | Springer |
ISSN | 1610-2940 |
Permalink - https://repository.rothamsted.ac.uk/item/8v246/structure-based-virtual-screening-of-hypothetical-inhibitors-of-the-enzyme-longiborneal-synthase-a-potential-target-to-reduce-fusarium-head-blight-disease