Methods of identification and Visualization of Tunnels for Flexible Ligands in Dynamic Proteins

supported by GACR, grant No. 17-07690S

Partner Research topics Key persons

University of West Bohemia, Faculty of Applied Sciences, Plzen, Czech Republic (UWB)

extraction of spatial information,
efficient data representation

prof. Dr. Ing. Ivana Kolingerová,
Ing. Martin Manak, Ph.D.

Masaryk University, Faculity of Informatics, Brno, Czech Republic (MUNI)

 visualization

doc. RNDr. Barbora Kozlíková, Ph.D.,
Ing. Adam Jurcik, Ph.D.

Czech Technical University in Prague, Faculty of Electrical Engineering, Prague, Czech Republic (ČVUT)

 motion planning

Ing. Martin Saska, Dr. rer. nat.,
Ing. Vojtech Vonasek, Ph.D.


Proteins are biochemical macromolecules perforrming crucial functions in all living organisms. Understanding protein function is important for faster invention of new drugs and other chemical compounds. Protein functions are highly influenced by their reactivity with other molecules (ligands). Performing a spatial analysis of ligands behavior in proteins under molecular dynamics is one of the most important current tasks in bioinformatics. Current approaches are mostly based on geometry, using a set of spheres and 3D geometrical subdivision. They work well for static models and simple molecules but for dynamic and complex molecular structures are not strong enough. Promising alternative solutions, utilizing sampling-based motion planning approaches, have appeared but sample the configuration space blindly, i.e. using uniform samples. The project aims to develop computational and visualization methods based on motion planning. The methods will work for flexible ligands moving in dynamic proteins.

Objectives:

  • Efficient extraction of spatial information to guide sampling of configuration space of a flexible ligand moving in a dynamic protein (UWB)
  • Motion planning using this spatial information (ČVUT)
  • Visualization of ligand movement (MUNI)
 
 
Example of an active site (denoted by the arrow) Examples of spherical tunnels (accessible pathways) leading towards the active site An example of a single trajectory inside one of these tunnels for a ligand

Publications:

  1. A Jurčík, K Furmanová, J Byška, V Vonásek, O Vávra, P Ulbrich, H Hauser and B Kozlíková. Visual Analysis of Ligand Trajectories in Molecular Dynamics. In 2019 IEEE Pacific Visualization Symposium (PacificVis) (). April 2019, 212-221. DOI BibTeX

    @inproceedings{jurcik2019visual,
	author = "A. {Jur\v{c}ík} and K. {Furmanová} and J. {By\v{s}ka} and V. {Vonásek} and O. {Vávra} and P. {Ulbrich} and H. {Hauser} and B. {Kozlíková}",
	booktitle = "2019 IEEE Pacific Visualization Symposium (PacificVis)",
	title = "Visual Analysis of Ligand Trajectories in Molecular Dynamics",
	year = 2019,
	volume = "",
	number = "",
	pages = "212-221",
	doi = "10.1109/PacificVis.2019.00032",
	issn = "2165-8765",
	month = "April"
}

  2. Katarína Furmanová, Barbora Kozlíková, Vojtěch Vonásek and Jan Byška. DockVis: Visual Analysis of Molecular Docking Data. In Barbora Kozlíková, Lars Linsen, Pere-Pau Vázquez, Kai Lawonn and Renata Georgia Raidou (eds.). Eurographics Workshop on Visual Computing for Biology and Medicine. 2019. DOI BibTeX

    @inproceedings{furmanova2019dockvis,
	booktitle = "Eurographics Workshop on Visual Computing for Biology and Medicine",
	editor = "Kozlíková, Barbora and Linsen, Lars and Vázquez, Pere-Pau and Lawonn, Kai and Raidou, Renata Georgia",
	title = "{DockVis: Visual Analysis of Molecular Docking Data}",
	author = "Furmanová, Katarína and Kozlíková, Barbora and Vonásek, Vojtěch and Byška, Jan",
	year = 2019,
	publisher = "The Eurographics Association",
	issn = "2070-5786",
	isbn = "978-3-03868-081-9",
	doi = "10.2312/vcbm.20191238"
}

  3. Vojtech Vonasek and Martin Saska. Increasing Diversity of Solutions in Sampling-based Path Planning. In Proceedings of the 2018 4th International Conference on Robotics and Artificial Intelligence. 2018, 97–102. URL PDF, DOI BibTeX

    @inproceedings{Vonasek:2018:IDS:3297097.3297114,
	author = "Vonasek, Vojtech and Saska, Martin",
	title = "Increasing Diversity of Solutions in Sampling-based Path Planning",
	booktitle = "Proceedings of the 2018 4th International Conference on Robotics and Artificial Intelligence",
	series = "ICRAI 2018",
	year = 2018,
	isbn = "978-1-4503-6584-0",
	location = "Guangzhou, China",
	pages = "97--102",
	numpages = 6,
	url = "http://doi.acm.org/10.1145/3297097.3297114",
	doi = "10.1145/3297097.3297114",
	acmid = 3297114,
	publisher = "ACM",
	address = "New York, NY, USA",
	keywords = "Path planning, Rapidly Exploring Random Tree",
	pdf = "data/papers/icrai2018_vonasek.pdf"
}

  4. V Vonásek, A Jurčík, K Furmanová and B Kozlíková. Sampling-Based Motion Planning for Tracking Evolution of Dynamic Tunnels in Molecular Dynamics Simulations. Journal of Intelligent & Robotic Systems, June 2018. URL, DOI BibTeX

    @article{vonasek2018sampling,
	author = "Von{\'a}sek, V. and Jur{\v{c}}{\'i}k, A. and Furmanov{\'a}, K. and Kozl{\'i}kov{\'a}, B.",
	title = "Sampling-Based Motion Planning for Tracking Evolution of Dynamic Tunnels in Molecular Dynamics Simulations",
	journal = "Journal of Intelligent {\&} Robotic Systems",
	year = 2018,
	month = "Jun",
	day = 16,
	issn = "1573-0409",
	doi = "10.1007/s10846-018-0877-6",
	url = "https://doi.org/10.1007/s10846-018-0877-6"
}

  5. V Vonasek and B Kozlikova. Tunnel detection in protein structures using sampling-based motion planning. In 2017 11th International Workshop on Robot Motion and Control (RoMoCo). July 2017, 185-192. PDF, DOI BibTeX

    @inproceedings{vonasek2017tunnel,
	author = "V. Vonasek and B. Kozlikova",
	booktitle = "2017 11th International Workshop on Robot Motion and Control (RoMoCo)",
	title = "Tunnel detection in protein structures using sampling-based motion planning",
	year = 2017,
	pages = "185-192",
	doi = "10.1109/RoMoCo.2017.8003911",
	pdf = "data/papers/romoco2017_vonasek.pdf",
	month = "July"
}

  6. Vojtech Vonasek and Barbora Kozlikova. Application of sampling-based path planning for tunnel detection in dynamic protein structures. In 2016 21st International Conference on Methods and Models in Automation and Robotics (MMAR). August 2016, 1010-1015. URL PDF, DOI BibTeX

    @inproceedings{vonasek2016application,
	author = "Vonasek, Vojtech and Kozlikova, Barbora",
	booktitle = "2016 21st International Conference on Methods and Models in Automation and Robotics (MMAR)",
	title = "Application of sampling-based path planning for tunnel detection in dynamic protein structures",
	year = 2016,
	pages = "1010-1015",
	keywords = "Atomic measurements;Cavity resonators;Collision avoidance;Probes;Proteins;Robots;Stability analysis",
	doi = "10.1109/MMAR.2016.7575276",
	month = "Aug",
	pdf = "data/papers/mmar2016protein.pdf",
	url = "http://ieeexplore.ieee.org/document/7575276/"
}