Thesis supervisor: András Szilágyi
Location of studies (in Hungarian): Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences (Magyar tudosok krt. 2, Budapest 1117) Abbreviation of location of studies: MTA
Description of the research topic:
Proteins are the key to all biochemical processes in living organisms. Although the structures of thousands of proteins have been determined by X-ray crystallography, we must think about proteins in terms of dynamic ensembles of structures rather than static structures. These structural ensembles are crucial to enzyme function, conformational changes, protein-ligand and protein-protein binding, and signal transduction processes within and between proteins.
Our research involves computational modeling of the structural ensembles, and describing protein function in terms of these ensembles. Although we use bioinformatic methods, we are part of an experimental group and do our work in close collaboration with experimentalists.
The structural ensembles and their changes can be described by energy landscapes and network models. On the energy landscape, the functional states of a protein correspond to basins separated by energy barriers; the depth of the basins and the height of the barriers may change during protein function, thus switching the system from one state to another. In the network models, the states are represented by the vertices of a graph, with the edges representing the possible transitions between the states.
Two distinct goals of the research are:
(1) To reveal the nature and general properties of structural ensembles and energy landscapes. To achieve this goal, we plan to characterize the energy landscapes of a number of different proteins. The project includes studying how disordered proteins become ordered upon binding.
(2) To describe the structural ensembles of proteins, mostly kinase enzymes, involved in regulatory processes and signal transduction within the cell, focusing particularly on structural changes occurring during signal transduction. For this project, we rely on, and help, experimental work being done in our group.
We model and study protein molecules by diverse computational methods. This includes dynamics simulation of models of various resolutions, and the analysis of simulation results by various mathematical methods. With regard to kinase enzymes, the project involves building interaction networks between kinases and their interacting partners, and structure prediction of complexes.
The research is supported by an OTKA grant, which also allows us to pay students.
Required language skills: English Further requirements: Basic knowledge of protein structure, basic programming knowledge, interest in theoretical approaches (modeling, mathematical methods, physics view)