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@article{1596878,
author = {Rangel Pamplona Pizarro Pinto, José Gaspar and Vávra, Ondřej and Filipovič, Jiří and Štourač, Jan and Bednář, David and Damborský, Jiří},
article_location = {LAUSANNE},
article_number = {OCT 29 2019},
doi = {http://dx.doi.org/10.3389/fchem.2019.00709},
keywords = {binding; docking; channel; unbinding; virtual screening; inhibitors; substrates; tunnel},
language = {eng},
issn = {2296-2646},
journal = {FRONTIERS IN CHEMISTRY},
title = {Fast Screening of Inhibitor Binding/Unbinding using Novel Software Tool CaverDock},
url = {https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2019/11/fchem19.pdf},
volume = {7},
year = {2019}
}
TY - JOUR
ID - 1596878
AU - Rangel Pamplona Pizarro Pinto, José Gaspar - Vávra, Ondřej - Filipovič, Jiří - Štourač, Jan - Bednář, David - Damborský, Jiří
PY - 2019
TI - Fast Screening of Inhibitor Binding/Unbinding using Novel Software Tool CaverDock
JF - FRONTIERS IN CHEMISTRY
VL - 7
IS - OCT 29 2019
SP - 1-14
EP - 1-14
PB - FRONTIERS MEDIA SA
SN - 22962646
KW - binding
KW - docking
KW - channel
KW - unbinding
KW - virtual screening
KW - inhibitors
KW - substrates
KW - tunnel
UR - https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2019/11/fchem19.pdf
L2 - https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2019/11/fchem19.pdf
N2 - Protein tunnels and channels are attractive targets for drug design. Drug molecules that block the access of substrates or release of products can be efficient modulators of biological activity. Here, we demonstrate the applicability of a newly developed software tool CaverDock for screening databases of drugs against pharmacologically relevant targets. First, we evaluated the effect of rigid and flexible side chains on sets of substrates and inhibitors of seven different proteins. In order to assess the accuracy of our software, we compared the results obtained from CaverDock calculation with experimental data previously collected with heat shock protein 90 alpha. Finally, we tested the virtual screening capabilities of CaverDock with a set of oncological and anti-inflammatory FDA-approved drugs with two molecular targets-cytochrome P450 17A1 and leukotriene A4 hydrolase/aminopeptidase. Calculation of rigid trajectories using four processors took on average 53 min per molecule with 90% successfully calculated cases. The screening identified functional tunnels based on the profile of potential energies of binding and unbinding trajectories. We concluded that CaverDock is a sufficiently fast, robust, and accurate tool for screening binding/unbinding processes of pharmacologically important targets with buried functional sites. The standalone version of CaverDock is available freely at https://loschmidt.chemi.muni.cz/caverdock/and the web version at https://loschmidt.chemi.muni.cz/caverweb/.
ER -
RANGEL PAMPLONA PIZARRO PINTO, José Gaspar, Ondřej VÁVRA, Jiří FILIPOVIČ, Jan ŠTOURAČ, David BEDNÁŘ and Jiří DAMBORSKÝ. Fast Screening of Inhibitor Binding/Unbinding using Novel Software Tool CaverDock. \textit{FRONTIERS IN CHEMISTRY}. LAUSANNE: FRONTIERS MEDIA SA, 2019, vol.~7, OCT 29 2019, p.~1-14. ISSN~2296-2646. Available from: https://dx.doi.org/10.3389/fchem.2019.00709.
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