Fast Screening of Inhibitor Binding/Unbinding Using Novel Software Tool CaverDock

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F19%3A00072466" target="_blank" >RIV/00159816:_____/19:00072466 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/19:00111903

Result on the web

<a href="https://www.frontiersin.org/articles/10.3389/fchem.2019.00709/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fchem.2019.00709/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fchem.2019.00709" target="_blank" >10.3389/fchem.2019.00709</a>

Result language

angličtina

Original language name

Fast Screening of Inhibitor Binding/Unbinding Using Novel Software Tool CaverDock

Original language description

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/.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10400 - Chemical sciences

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Chemistry

ISSN

2296-2646

e-ISSN

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Volume of the periodical

7

Issue of the periodical within the volume

October

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

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UT code for WoS article

000497430300001

EID of the result in the Scopus database

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