Research - Institute of Biophysics - Laboratory of Energy Converting Redox Enzymes - Structural Bioinformatics of Bioactive Peptides/Molecules

Gábor RÁKHELY
Principal Investigator

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Balázs LEITGEB
Principal Investigator

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Liza HUDOBA PhD Student

STRUCTURAL BIOINFORMATICS OF BIOACTIVE PEPTIDES/MOLECULES

Bioactive peptides are a group of diverse intercellular signalling molecules. Almost half a century of research on this topic has resulted in an enormous amount of data. Bacteria, fungi or higher eukaryotic cells and tissues express a variety of biologically active peptides and these cell lines are also able to respond to many different bioactive peptides, indicating that multiple receptors and signal transduction pathways are present in a single cell. Bioactive peptides might have very diverse effects: they might be antimicrobials, or serve as signalling molecules which are involved in development, cellular responses or control processes.

Numerous neurodegenerative diseases are related to conformational changes and/or aggregation of small proteins or peptides, such as polyalanine or polyglutamine. The molecular mechanisms of their action might also vary: they can aspecifically interact with the membrane, but more typically, they are bound by specific receptors. Usually, the interaction of these peptides with their receptors requires special conformation of the partners. The bioactive conformation of a peptide can be studied by few experimental methods, but cheap and powerful computer-based approaches are also available to explore the conformational space of a given molecule, to identify the intramolecular interactions stabilizing the structure and to describe the molecular events in time. The peptide – receptor interaction can be further characterized by in silico docking, provided the 3D structure of the receptor is available.




The prediction of a bioactive conformation allows us to get a deeper insight into the molecular basis of biological processes and to design new peptidomimetic compounds/drugs for therapeutic purposes.

In the last few years we studied bioactive peptides either related to neurodegenerative disorders or having antimicrobial effects. We disclosed the secondary structures of homopolyamino acids, especially polyalanine and polyglutamine, whose aggregation seems to be related to neurodegenerative disorders such as Alzheimer’s disease. Molecular dynamics calculations were performed to simulate the temporal folding processes. Additionally, in silico structural analyses were performed for cyclic nonapeptides, conopressins having neuromodulator effects. Among the antimicrobial peptides we explored the conformational space of indolicidin and other molecules of palindromic structure. These studies might form the basis to design new antimicrobial drugs, which can be generally used for protecting human health.

Selected publications

Leitgeb, B., Szekeres, A., Manczinger, L., Vágvölgyi, C. and Kredics, L. (2007). The history of alamethicin: A review of the most extensively studied peptaibol. Chem. Biodiv. 4(6): 1027-1051.

Leitgeb, B., Kerényi, Á., Bogár, F., Paragi, G., Penke, B. and Rákhely, G. (2007). Studying the structural properties of polyalanine and polyglutamine peptides. J. Mol. Model. 13(11): 1141-1150.

Leitgeb, B. (2007). Structural investigation of endomorphins by experimental and theoretical methods: Hunting for the bioactive conformation. Chem. Biodiv. 4(12): 2703-2724.

Janzsó, G., Rákhely, G. and Leitgeb, B. (2009). Comprehensive structural characterization of the cyclic disulphide-bridged nonapeptides, Arg- and Lys-conopressins. J. Mol. Graph. Model. 27(8): 881-888.