VÁVRA, Ondřej, Jiří FILIPOVIČ, Jan PLHÁK, David BEDNÁŘ, Sérgio Manuel MARQUES, Jan BREZOVSKÝ, Jan ŠTOURAČ, Luděk MATYSKA and Jiří DAMBORSKÝ. CaverDock: a molecular docking-based tool to analyse ligand transport through protein tunnels and channels. Bioinformatics, Oxford: Oxford University Press, 2019, vol. 35, No 23, p. 4986-4993. ISSN 1367-4803. doi:10.1093/bioinformatics/btz386.
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Basic information
Original name CaverDock: a molecular docking-based tool to analyse ligand transport through protein tunnels and channels
Name in Czech CaverDock: na molekulovém dokingu založený nástroj k analýze transportu ligandu skrz tunely a kanály v proteinech
Authors VÁVRA, Ondřej (203 Czechia, belonging to the institution), Jiří FILIPOVIČ (203 Czechia, guarantor, belonging to the institution), Jan PLHÁK (203 Czechia, belonging to the institution), David BEDNÁŘ (203 Czechia, belonging to the institution), Sérgio Manuel MARQUES (620 Portugal, belonging to the institution), Jan BREZOVSKÝ (203 Czechia, belonging to the institution), Jan ŠTOURAČ (203 Czechia, belonging to the institution), Luděk MATYSKA (203 Czechia, belonging to the institution) and Jiří DAMBORSKÝ (203 Czechia, belonging to the institution).
Edition Bioinformatics, Oxford, Oxford University Press, 2019, 1367-4803.
Other information
Original language English
Type of outcome article in a journal
Field of Study 10602 Biology , Evolutionary biology
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW Full Text
Impact factor Impact factor: 5.610
RIV identification code RIV/00216224:14310/19:00110114
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1093/bioinformatics/btz386
UT WoS 000506808900016
Keywords in English HALOALKANE DEHALOGENASE LINB; ENERGY LANDSCAPE; ACTIVE-SITE; DYNAMICS; MECHANISM; BINDING; RECOGNITION; KINETICS
Tags J-D1, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Marie Šípková, DiS., učo 437722. Changed: 24/3/2020 12:47.
Abstract
Motivation Protein tunnels and channels are key transport pathways that allow ligands to pass between proteins’ external and internal environments. These functionally important structural features warrant detailed attention. It is difficult to study the ligand binding and unbinding processes experimentally, while molecular dynamics simulations can be time-consuming and computationally demanding. Results CaverDock is a new software tool for analysing the ligand passage through the biomolecules. The method uses the optimized docking algorithm of AutoDock Vina for ligand placement docking and implements a parallel heuristic algorithm to search the space of possible trajectories. The duration of the simulations takes from minutes to a few hours. Here we describe the implementation of the method and demonstrate CaverDock’s usability by: (i) comparison of the results with other available tools, (ii) determination of the robustness with large ensembles of ligands and (iii) the analysis and comparison of the ligand trajectories in engineered tunnels. Thorough testing confirms that CaverDock is applicable for the fast analysis of ligand binding and unbinding in fundamental enzymology and protein engineering.
Abstract (in Czech)
Motivace Tunely a kanály v proteinech jsou klíčové transportní cesty, které umožňují ligandům projít mezi vnějším a vnitřním prostředí proteinu. Tyto funkčně důležité strukturní vlastnosti přitahují detailní pozornost. Experimentální studium navázání a odchodu ligandu je složité, zatímco studium pomocí molekulové dynamiky může být časově a výpočetně náročné. Výsledky CaverDock je nový softwareový nástroj pro analýzu průchodu ligandu skrz biomolekuly. Tato metoda využívá optimalizovaný dokovací algoritmus z AutoDock Vina pro umístění ligandu a implementuje paralelní heuristický algoritmus k prohledávání prostoru možných trajektorií. Čas simulací vyžaduje od munut po několik hodin. V tomto článku vysvětlujeme implementaci metody a demonstrujeme použitelnost CaverDocku pomocí: (i) porovnání výsledků s ostatními dostupnými nástroji, (ii) určení robustnosti na velkém ensamblu ligandů a (iii) analýzy a porovnání trajektorií ligandu v uměle modifikovaných tunelech. Testování potvrzuejže CaverDock je použitelný pro rychlou analýzu navázání a odchodu ligandu ve fundamentální enzymologii a proteinovém inženýrství.
Links
EF16_013/0001761, research and development projectName: RECETOX RI
LM2015047, research and development projectName: Česká národní infrastruktura pro biologická data (Acronym: ELIXIR-CZ)
Investor: Ministry of Education, Youth and Sports of the CR, Large Infrastructures for Research, Development and Innovation
LM2015055, research and development projectName: Centrum pro systémovou biologii (Acronym: C4SYS)
Investor: Ministry of Education, Youth and Sports of the CR, Large Infrastructures for Research, Development and Innovation
LM2015085, research and development projectName: CERIT Scientific Cloud (Acronym: CERIT-SC)
Investor: Ministry of Education, Youth and Sports of the CR, Large Infrastructures for Research, Development and Innovation
814418, internal MU codeName: Synthetic biology-guided engineering of Pseudomonas putida for biofluorination (Acronym: SinFonia)
Investor: European Union, Horizon 2020, Leadership in enabling and industrial technologies (LEIT) (Industrial Leadership)
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