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.

Basic information

Original name

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

Authors

RANGEL PAMPLONA PIZARRO PINTO, José Gaspar (620 Portugal, belonging to the institution), Ondřej VÁVRA (203 Czech Republic, belonging to the institution), Jiří FILIPOVIČ (203 Czech Republic, belonging to the institution), Jan ŠTOURAČ (203 Czech Republic, belonging to the institution), David BEDNÁŘ (203 Czech Republic, belonging to the institution) and Jiří DAMBORSKÝ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10400 1.4 Chemical sciences

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.693

RIV identification code

RIV/00216224:14310/19:00111903

Organization unit

Faculty of Science

DOI

UT WoS

000497430300001

Keywords in English

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

Tags

Tags

International impact, Reviewed
Změněno: 15/2/2023 22:25, Mgr. Michaela Hylsová, Ph.D.

Abstract

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/.

Links

EF16_013/0001761, research and development project
Name: RECETOX RI
LM2015047, research and development project
Name: Česká národní infrastruktura pro biologická data (Acronym: ELIXIR-CZ)
Investor: Ministry of Education, Youth and Sports of the CR, Czech National Infrastructure for Biological Data
LM2015051, research and development project
Name: Centrum pro výzkum toxických látek v prostředí (Acronym: RECETOX RI)
Investor: Ministry of Education, Youth and Sports of the CR
LM2015055, research and development project
Name: Centrum pro systémovou biologii (Acronym: C4SYS)
Investor: Ministry of Education, Youth and Sports of the CR
LM2015085, research and development project
Name: CERIT Scientific Cloud (Acronym: CERIT-SC)
Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud