Dr. Michael Ramek: Research.

deutsche Version.

Main research activity is the structure determination of biologically important compounds via quantum chemical ab initio methods.

For several years the focus had been on intramolecular hydrogen bonds in amino- and hydroxy compounds (FWF-projects P6856 (1988-1990), P8053 (1990-1991), and P9095 (1992-1994)); the results of these studies have found application, e.g., in the field of shape-similarity analysis in cooperation with Prof. Paul G. Mezey (University of Saskatchewan, Saskatoon, Canada). In the recent years the main targets are derivatives of indole-3-acetic acid and model peptides (see below).

For a number of years the symmetrization of wavefunctions and quantum states has been investigated in a series of publications, most of them in cooperation with Prof. Bruno Gruber(Southern Illinois University, Carbondale, IL (USA)).

Indole-3-acetic acid and its derivatives are growth hormones in plants (auxins), which govern many biological processes such as cell divisions and enlargement, developmental differentiation, and the syntheses of specific proteins. In a series of papers, co-authored by Dr. Sanja Tomić (Institut Ruđer Bošković, Zagreb, Croatia), it could be shown that the potential energy surfaces of these compounds are very sensitive to substitution at a specific position of the indole nucleus (position 4), whereas substitution by ethyl or chlorine at the other positions of the phenyl ring has no influence on the potential energy surfaces. Although the form of the potential energy surface cannot be directly correlated with biological activity, because other factors (lipophilicity or correlation with other compounds like cytokinines) are also of importance, these studies give important clues to the forces that determine auxin activity.

Peptides are mostly modeled by attaching a formyl or acetyl group to the N-terminus of a short peptide chain and by converting the C-terminus to an amide group at the same time. The peptide chain may as small as a single residue X, in which case the model compound HCO-X-NH₂ or CH₃CO-X-NH₂ contains two peptide bonds and thus is called a model dipeptide. Model dipeptides can be used to study interactions of one amino acid residue with its next nearest neighbour (1-3-interactions) like γ-turns; analogously, model tripeptides of the type HCO-X-Y-NH₂ can be used to model 1-4-interactions like β-turns. Model dipeptides have been often used as structure paradigms for larger peptides, in some cases with remarkable success. Using the example of HCO-L-Ala-L-Ala-NH₂, it could be shown in collaboration with Prof. Lothar Schäfer and Ching-Hsing Yu (University of Arkansas, Fayetteville, AR, USA) that this dipeptide approximation, however, is a dangerous approach and considerably longer model peptides will be necessary to predict overall protein structures properly.