Improving ligand transport trajectory within flexible receptor
in CaverDock

D 2022

Improving ligand transport trajectory within flexible receptor in CaverDock

NĚMCOVÁ, Petra, Jana HOZZOVÁ a Jiří FILIPOVIČ

Základní údaje

Originální název

Improving ligand transport trajectory within flexible receptor in CaverDock

Autoři

NĚMCOVÁ, Petra (203 Česká republika, domácí), Jana HOZZOVÁ (703 Slovensko, domácí) a Jiří FILIPOVIČ (203 Česká republika, garant, domácí)

Vydání

USA, SAC '22: Proceedings of the 37th ACM/SIGAPP Symposium on Applied Computing, od s. 619-626, 8 s. 2022

Nakladatel

Association for Computing Machinery

Další údaje

Jazyk

angličtina

Typ výsledku

Stať ve sborníku

Obor

10201 Computer sciences, information science, bioinformatics

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Forma vydání

elektronická verze "online"

Odkazy

URL

Kód RIV

RIV/00216224:14610/22:00125815

Organizační jednotka

Ústav výpočetní techniky

ISBN

978-1-4503-8713-2

DOI

http://dx.doi.org/10.1145/3477314.3506988

UT WoS

000946564100083

Klíčová slova anglicky

CaverDock; ligand transport; flexible receptor; molecular docking; search heuristic; continuous space search

Štítky

core_B, firank_A, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 2. 2024 16:11, Mgr. Marie Šípková, DiS.

Anotace

V originále

The receptor-ligand interactions are an important part of many biologically relevant processes. The small ligand molecule needs to pass via a tunnel into a receptor before the interaction of interest begins. Both receptor-ligand interaction and ligand pathway need to be studied. CaverDock is a computational tool that simulates the transport of the ligand in a tunnel. However, in its first version, CaverDock allowed only limited flexibility of the receptor, biasing the measured energy of ligand transportation. In this paper, we introduce two essential extensions to CaverDock. First, we combine its force field with AMBER, which allows to relax receptor’s geometry in tunnel bottlenecks. Second, we improve CaverDock heuristics for ligand trajectory search to obtain multiple variants of ligand trajectories, ideally with lower energy compared to the result of CaverDock 1.0. We experimentally demonstrate that the new heuristic is superior to the original one and that the receptor relaxation improves precision of CaverDock results.

Návaznosti

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

MUNI/A/1145/2021, interní kód MU

Název: Rozsáhlé výpočetní systémy: modely, aplikace a verifikace XI. (Akronym: SV-FI MAV XI.)

Investor: Masarykova univerzita, Rozsáhlé výpočetní systémy: modely, aplikace a verifikace XI.

Citovat

NĚMCOVÁ, Petra, Jana HOZZOVÁ a Jiří FILIPOVIČ. Improving ligand transport trajectory within flexible receptor in CaverDock. Online. In SAC '22: Proceedings of the 37th ACM/SIGAPP Symposium on Applied Computing. USA: Association for Computing Machinery, 2022, s. 619-626. ISBN 978-1-4503-8713-2. Dostupné z: https://dx.doi.org/10.1145/3477314.3506988.

@inproceedings{1853582,
   author = {Němcová, Petra and Hozzová, Jana and Filipovič, Jiří},
   address = {USA},
   booktitle = {SAC '22: Proceedings of the 37th ACM/SIGAPP Symposium on Applied Computing},
   doi = {http://dx.doi.org/10.1145/3477314.3506988},
   keywords = {CaverDock; ligand transport; flexible receptor; molecular docking; search heuristic; continuous space search},
   howpublished = {elektronická verze "online"},
   language = {eng},
   location = {USA},
   isbn = {978-1-4503-8713-2},
   pages = {619-626},
   publisher = {Association for Computing Machinery},
   title = {Improving ligand transport trajectory within flexible receptor in CaverDock},
   url = {https://dl.acm.org/doi/10.1145/3477314.3506988},
   year = {2022}
}

TY  - JOUR
ID  - 1853582
AU  - Němcová, Petra - Hozzová, Jana - Filipovič, Jiří
PY  - 2022
TI  - Improving ligand transport trajectory within flexible receptor in CaverDock
PB  - Association for Computing Machinery
CY  - USA
SN  - 9781450387132
KW  - CaverDock
KW  - ligand transport
KW  - flexible receptor
KW  - molecular docking
KW  - search heuristic
KW  - continuous space search
UR  - https://dl.acm.org/doi/10.1145/3477314.3506988
N2  - The receptor-ligand interactions are an important part of many biologically relevant processes. The small ligand molecule needs to pass via a tunnel into a receptor before the interaction of interest begins. Both receptor-ligand interaction and ligand pathway need to be studied. CaverDock is a computational tool that simulates the transport of the ligand in a tunnel. However, in its first version, CaverDock allowed only limited flexibility of the receptor, biasing the measured energy of ligand transportation. In this paper, we introduce two essential extensions to CaverDock. First, we combine its force field with AMBER, which allows to relax receptor’s geometry in tunnel bottlenecks. Second, we improve CaverDock heuristics for ligand trajectory search to obtain multiple variants of ligand trajectories, ideally with lower energy compared to the result of CaverDock 1.0. We experimentally demonstrate that the new heuristic is superior to the original one and that the receptor relaxation improves precision of CaverDock results.
ER  -

NĚMCOVÁ, Petra, Jana HOZZOVÁ a Jiří FILIPOVIČ. Improving ligand transport trajectory within flexible receptor in CaverDock. Online. In \textit{SAC '22: Proceedings of the 37th ACM/SIGAPP Symposium on Applied Computing}. USA: Association for Computing Machinery, 2022, s.~619-626. ISBN~978-1-4503-8713-2. Dostupné z: https://dx.doi.org/10.1145/3477314.3506988.

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