The precise determination of the nature and energetics of intra- and inter-molecular non-covalent interactions of biomolecules is crucial for understanding the structural organization and function of biomolecular systems. In this contribution the studies of non-covalent interactions involved in the protein folding process and formation of ligand-receptor complexes were presented. The first are related to the challenge of predicting folded structure from the protein sequence alone and the second to the need of novel therapeutic agents. Our NMR studies resulted in new important findings, which contribute to the understanding of the early stages of protein folding. The advantages of NMR methods for detection and characterization of the ligand-receptor interactions and their ability to provide a combined structure-dynamic insight into ligand binding modes were used to discover novel inhibitors of various protein targets. The importance of identification of dynamic processes and investigation of their influence on the stability of ligand-receptor interactions as well as on the inhibitory activities of novel ligands were highlighted. Results provide important aspect for the design of new drug leads.
B.04 Guest lecture
COBISS.SI-ID: 5352986By applying infrared spectroscopy, we have gained the insights into peptide secondary structures through assignation of the amide bands for different conformations of the model peptide poly-L-lysine (PLL). In water at low pH values, PLL mainly possessed the PII and β structures, while at higher pH values and low temperatures, characteristic band for the α-helical conformation was found. The increase in temperature induced the formation of β structures that are components of amyloid fibrils. The therapeutic importance of gaining a detailed knowledge on insulin fibrillation in relation to type I diabetes has led to intensive studies focusing on its fibrillation kinetics and structural characteristics. Insulin fibrils feature the characteristics that are common to all amyloid fibrils, such as an elongated, unbranched morphology, characteristic cross-β diffraction pattern and Thioflavin T fluorescence. The kinetic parameters were comparable to those obtained with Thioflavin T fluorescent measurements. We observed the melting of α-helix and PII conformation of native insulin with the formation of β-sheets.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 267472384Jože Grdadolnik spent three months at University of Cagliari (Sardinia, Italy) as visiting professor. He lectured themes from vibrational spectroscopy of biological molecules to undergraduate and doctoral students of chemistry and biochemistry at Faculty of Chemistry and Geology (2 ECTS).
B.05 Guest lecturer at an institute/university
From the year 2007, we cooperate with Krka d. d. (pharmaceutical industry) by developing new analytical tools based on the vibrational spectroscopy and modern chemometric methods. The cooperation is based on annual contracts.
F.10 Improvements to an existing technological process or technology
F. Merzel coordinates the initiative of Slovenian researchers for formal membership of Slovenia in the consortium of the central European countries (CENI) providing the partnership for neutron scattering research at the Institute Laue Langevin, Grenoble.
D.03 Membership in foreign/international boards/committees