Loschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University
Understanding protein-ligand interactions is crucial in many biochemical disciplines, such as drug design or enzyme engineering. In a project of Grant Agency of Masaryk University (MUNI/M/1888/2014), we are developing a novel method and tool for analysis of transport processes. Our method uses modified molecular docking based on Autodock Vina, which docks a ligand using constraints allowing precise definition of the position in the protein cavity. By iterative docking of the ligand along the protein cavity, we obtain its trajectory and also energy profile. We use a heuristic algorithm to determine the constraints for molecular docking, thus much less protein-ligand conformations are evaluated than in the case of molecular dynamics, resulting in the faster simulation.
Our method is being implemented in CaverDock tool, which uses geometrical tunnels from well-known software Caver as an input and docks a ligand into the tunnel by using our modified docking algorithm. The CaverDock is very easy to setup and needs significantly less computational time comparing to methods based on molecular dynamics, whereas it is still able to return trajectory of ligand movement and energetic profile of the transport process.
Results
- CaverDock software
- Jiří Filipovič, Ondřej Vávra, Jan Plhák, David Bednář, Sérgio M. Marques, Jan Brezovský, Luděk Matyska, Jiří Damborský. CaverDock: a novel method for the fast analysis of ligand transport. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2019.
- Ondřej Vávra, Jiří Filipovič, Jan Plhák, David Bednář, Sérgio M. Marques, Jan Brezovský, Jan Štourač, Luděk Matyska, Jiří Damborský. averDock: a molecular docking-based tool to analyse ligand transport through protein tunnels and channels. Bioinformatics, Vol. 35, Issue 23, 2019.
- Jan Štourač, Ondřej Vávra, Piia Kokkonen, Jiří Filipovič, Gaspar Pinto, Jan Brezovský, Jiří Damborský, David Bednář. Caver Web 1.0: identification of tunnels and channels in proteins and analysis of ligand transport. Nucleic acids research, Vol. 47, Issue W1, 2019.
- Gaspar Pinto, Ondřej Vávra, Jiří Filipovič, Jan Štourač, David Bednář, Jiří Damborský. Fast Screening of Inhibitor Binding/Unbinding Using Novel Software Tool CaverDock. Frontiers in chemistry, 2019.
This work was supported by the project GAMU Pokročilé hybridní metody studia transportních procesů v proteinech a jejich využití v designu biokatalyzátorů MUNI/M/1888/2014
