Improving ligand transport trajectory within flexible receptor
in CaverDock

D 2022

Improving ligand transport trajectory within flexible receptor in CaverDock

NĚMCOVÁ, Petra, Jana HOZZOVÁ and Jiří FILIPOVIČ

Basic information

Original name

Improving ligand transport trajectory within flexible receptor in CaverDock

Authors

NĚMCOVÁ, Petra (203 Czech Republic, belonging to the institution), Jana HOZZOVÁ (703 Slovakia, belonging to the institution) and Jiří FILIPOVIČ (203 Czech Republic, guarantor, belonging to the institution)

Edition

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

Publisher

Association for Computing Machinery

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

10201 Computer sciences, information science, bioinformatics

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Publication form

electronic version available online

References:

URL

RIV identification code

RIV/00216224:14610/22:00125815

Organization unit

Institute of Computer Science

ISBN

978-1-4503-8713-2

DOI

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

UT WoS

000946564100083

Keywords in English

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

Abstract

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.

Links

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1145/2021, interní kód MU

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

Investor: Masaryk University

Citovat

NĚMCOVÁ, Petra, Jana HOZZOVÁ and 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, p. 619-626. ISBN 978-1-4503-8713-2. Available from: 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 and 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, p.~619-626. ISBN~978-1-4503-8713-2. Available from: https://dx.doi.org/10.1145/3477314.3506988.

Detailed Information on Publication Record