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

J 2019

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

RANGEL PAMPLONA PIZARRO PINTO, José Gaspar, Ondřej VÁVRA, Jiří FILIPOVIČ, Jan ŠTOURAČ, David BEDNÁŘ et. al.

Základní údaje

Originální název

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

Autoři

RANGEL PAMPLONA PIZARRO PINTO, José Gaspar (620 Portugalsko, domácí), Ondřej VÁVRA (203 Česká republika, domácí), Jiří FILIPOVIČ (203 Česká republika, domácí), Jan ŠTOURAČ (203 Česká republika, domácí), David BEDNÁŘ (203 Česká republika, domácí) a Jiří DAMBORSKÝ (203 Česká republika, garant, domácí)

Vydání

FRONTIERS IN CHEMISTRY, LAUSANNE, FRONTIERS MEDIA SA, 2019, 2296-2646

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10400 1.4 Chemical sciences

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Full Text

Impakt faktor

Impact factor: 3.693

Kód RIV

RIV/00216224:14310/19:00111903

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.3389/fchem.2019.00709

UT WoS

000497430300001

Klíčová slova anglicky

binding; docking; channel; unbinding; virtual screening; inhibitors; substrates; tunnel

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 2. 2023 22:25, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

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/.

Návaznosti

EF16_013/0001761, projekt VaV

Název: RECETOX RI

LM2015047, projekt VaV

Název: Česká národní infrastruktura pro biologická data (Akronym: ELIXIR-CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Česká národní infrastruktura pro biologická data

LM2015051, projekt VaV

Název: Centrum pro výzkum toxických látek v prostředí (Akronym: RECETOX RI)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Výzkumná infrastruktura RECETOX

LM2015055, projekt VaV

Název: Centrum pro systémovou biologii (Akronym: C4SYS)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, The national infrastructure C4SYS - Centre for Systems Biology

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

Citovat

RANGEL PAMPLONA PIZARRO PINTO, José Gaspar, Ondřej VÁVRA, Jiří FILIPOVIČ, Jan ŠTOURAČ, David BEDNÁŘ a Jiří DAMBORSKÝ. Fast Screening of Inhibitor Binding/Unbinding using Novel Software Tool CaverDock. FRONTIERS IN CHEMISTRY. LAUSANNE: FRONTIERS MEDIA SA, 2019, roč. 7, OCT 29 2019, s. 1-14. ISSN 2296-2646. Dostupné z: https://dx.doi.org/10.3389/fchem.2019.00709.

@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 a Jiří DAMBORSKÝ. Fast Screening of Inhibitor Binding/Unbinding using Novel Software Tool CaverDock. \textit{FRONTIERS IN CHEMISTRY}. LAUSANNE: FRONTIERS MEDIA SA, 2019, roč.~7, OCT 29 2019, s.~1-14. ISSN~2296-2646. Dostupné z: https://dx.doi.org/10.3389/fchem.2019.00709.

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