Group leader: Prof. Istvan Simon
The genome projects
have significantly extended the scope of investigated proteins.
First, transmembrane proteins have been shown to be of much higher
proportion among proteins than ever thought before. Later the
existence of partially or fully disordered proteins and their
surprisingly high representation in eukaryotic organisms have been
detected, as well as their key role in signal transduction and
regulation processes. Our group applies and develops theoretical and
computational tools to investigate the organization of functionally
relevant states and stability of proteins, as well as the physical
background of their functionality. We are keeping up with new
scientific trends and our group is engaged in the research of
globular, transmembrane and disordered proteins. Last, but not least
significant efforts are made to clarify the basic principles
determining proteins’ physiologically relevant states. The results
have not only been published in journals but also over a dozen web
servers were established for structure analysis and prediction.
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We have been engaged in the research of the largest protein family since our group has been established. Numerous structure prediction methods have been developed based on protein sequence and structure analysis; such methods can be found on the CYSREDOX web server for the prediction of cystein residues participating in disulphide bonds. The concept of stabilization centers has been introduced for non-covalent crosslink playing a dominant role in protein structure stability. A new method has been developed for the prediction and identification of amino acids in these centers based on the amino acid sequence and on the protein structure, respectively (i.e. SCide, SCpred, SRide web servers). Among others, these results have been successfully applied for the analysis of the functionally regulated stability of MHC proteins and of the properties of TIM barrel structural elements, respectively, as well as for the demonstration of the divergent evolution of PD-(D/E)XK restriction endonucleases. The structural properties of several proteins have been determined by molecular mechanical and molecular dynamical tools. The role of the hydration sphere in protein – DNA recognition processes has been shown. Also, the role of metal ions in the functionality of endonucleases has been identified. Our most recent results are in the development of novel methodology for the modeling of biochemical reactions.
Our most recognized achievement of the past five years was the realization that disordered proteins have a higher mean energy than globular proteins. Based on this observation the partially or fully disordered proteins or protein segments can be distinguished using the protein sequence alone (see IUPred web server).
It allowed to gain valuable insight concerning the intermolecular interactions of disordered proteins. This includes the uncovering of the role preformed structural elements and certain motifs play in protein-protein interactions. Furthermore, it enabled the verification of the abundance of disordered proteins among hubs in protein interaction networks and the significantly high occurrence of protein disorder in essential proteins. These fundamental results enabled the characterization of interacting regions in disordered proteins and the development of a prediction method called ANCHOR for the prediction of such disordered binding sites. We have also demonstrated the functional role of protein disorder in numerous cases, including the analysis of the dUTPase and transglutaminase substrate preference and the mediator complex involved in transcriptional regulation.