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Protein Structure Research Group

 Leader: Prof. István Simon, PhD, DSc


-        Csaba Magyar, PhD, research fellow

-        Bálint Mészáros, PhD, research fellow

-        Erzsébet Fichó, junior research fellow

-        Rózsa Fütő, junior research fellow


The group’s main area of research is the computational study of the link between protein structure and intrinsic protein disorder, and protein interactions. Apart from theoretical and bioinformatics studies, conducted research also covers the study of biological functions and their possible modulations with the use of docking techniques.

Main research areas:

 Globular proteins

The group has been involved in the research of ordered, globular proteins since its foundation. Based on sequence studies, several prediction algorithms were developed, such as the CYSREDOX web server aimed at the identification of cysteines in disulphide bonds. The concept of stabilization centers was developed in the group with the aim of describing non-covalent bonding forces in globular structures. Apart from the theoretical foundation, the web servers serving as prediction tools for stabilization-centers were also constructed (SCide, SCpred, SRide web servers). Complementing these theoretical works, the structural properties of various proteins were determined by molecular mechanics/dynamics studies as well. This approach was implemented in the modeling of drug target proteins as well with the use of vHTS (virtual high throughput screening) calculations, while – in parallel – developing and testing virtual screening protocols, applicable in large-scale studies.

Transmembrane proteins

By the second half of the 90′s the focus of the group’s research has shifted towards transmembrane (TM) proteins. It has been shown that the alignment of transmembrane proteins required specialized methods. Furthermore, it also has been shown that the topology of TM proteins corresponds to a maximal likelihood state that is identifiable with hidden Markov models from the sequence. These realizations gave way to the construction of the widely used DAS, DAS-TMfilter and HMMTOP prediction methods. Furthermore, the group has also developed an algorithm capable of the determination of the position of the bilipid membrane from the structure of TM proteins (TMDET server). This algorithm is the basis of the weekly updated PDB_TM database. In addition, two more databases were also developed: TOPDB and TOPDOM, which contain chemical and biochemical data. All three databases are equipped with search engines and are publicly available through the internet. Apart from these theoretical and methodological works, the group has conducted significant research concerning ABC transporters and has uncovered the transmembrane origins of the prion protein.

Disordered proteins and their interactions

 The most prominent research conducted in the group in later years covers the study of intrinsically disordered proteins (IDPs). These proteins do not adopt a stable 3D structure even under native conditions, however they fulfill crucial biological roles. The group’s most significant contributions to the field was the construction of IUPred, a method to identify IDPs based on their sequences, and the construction of ANCHOR that aims the sequence-based identification of interacting sites in IDPs. Both methods are based on low resolution force fields, termed statistical potentials that effectively capture the main biophysical interactions between amino acid residues that govern both the folding and the binding of these proteins. Furthermore, both methods are offered as a publicly accessible web servers.

The current focus of the group is the analysis of interactions formed between disordered proteins. In the past, the group has already addressed the description of the interactions between ordered and disordered proteins. However, there exist so-called two state protein complexes which are formed by disordered monomers and become ordered upon interaction. The statistical physics description of these systems is one of the main problems currently addressed by the Protein Structure Research Group. This ordering process is analogous to the hydrophobic collapse during folding and consequently the uncovering of the physical process behind it will serve as a bridge between the description of the structure formation of ordered and disordered proteins. Furthermore, the description of the water-immersed regions of transmembrane proteins will provide a similar bridging role between the description of structure formation in the water and the membrane phases. The completion of these tasks will open the way for the development of a unified description of protein structure formation in general.


The group has collaborations with sever outstanding Hungarian and international groups and research institutes.