PhD position in Visualization and visual analysis of tunnels for flexible ligands in protein dynamics

Proteins are biochemical macromolecules, performing crucial functions in all living organisms. Understanding their function is critical for the process of targeted mutagenesis, leading to faster invention of new drugs and other chemical compounds. Protein function is highly influenced by its chemical reactions with other molecules (ligands), localized in socalled active sites, void spaces often hidden deeply inside a protein. They are connected with an outside solvent via tunnels representing the paths along which a ligand can reach the active site. Recent studies confirmed that the protein function is highly dependent on the protein dynamics. Thus, performing the spatial analysis of proteins in MD (molecular dynamics), in particular studying the tunnels, becomes one of the most important current tasks in bioinformatics.

Currently available algorithms and systems for tunnel detection are based on Voronoi diagrams. The main limitation is that these techniques are not dealing with the actual ligand transportation, i.e., they are not detecting tunnels according to ligand shape and orientation. To overcome this, we propose an alternative solution to tunnel detection when we formulate the tunnel detection task as a motion planning problem for a many-DOF robot – a search in a high-dimensional configuration space, explored using sampling-based methods. The configuration space is randomly sampled to build a roadmap graph of collision-free configurations. Protein dynamics can be introduced through the collision detection computed considering actual positions of atoms in the given frame. A path in the roadmap then corresponds to the final plan or tunnel in the case of tunnel detection.

The visual representation of detected tunnels and ligand passages currently shows the animation of ligand transport through a tunnel represented by a set of spheres or a tunnel surface. This is slow for long MD simulations as the exploration of individual snapshots is very lengthy and it is hard to perceive all related aspects, such as the physico-chemical properties of the amino-acids surrounding the tunnel and interacting with the ligand. Therefore, it is necessary to come with specific representations focusing on these different aspects and presenting them in a comprehensible way.

Within this project, you will focus on the following topics:
1. How to visually represent the results of ligand transportation through a tunnel detected by the motion planning approach.
2. How to enhance the communication of interesting and important events happening within the molecular dynamics simulations (again, using visualization).
3. Propose a visual analysis tool for exploration of ligand passage and its main properties.

This project runs in collaboration with computer graphists at the University of West Bohemia in Pilsen, members of the robotics group at the Czech Technical University in Prague, and protein engineers from the Masaryk University in Brno.

The successful candidate is supposed to have his or her degree in Computer Graphics, with some experience in visualization.

Required knowledge: Java, OpenGL

The position is funded from the project of the Czech Grant Agency.
Informal inquiries can be made to Dr. Barbora Kozlikova ([Email Address Removed]) with a copy of your CV and cover letter.