Computational Biochemistry

Reaction Mechanisms

The fact that exposure of living matter to ionizing radiation causes damage to DNA, with bioradicals (base or sugar radicals) as primary products that consequently lead to chain breaks and DNA-DNA or DNA-protein cross-links, is beyond dispute. Therefore, elucidation of the identity of the radicals is of vital importance due to our exposure to cosmic rays, natural radioactive elements and X-rays. Many biologically related processes occur through free bioradical pathways. Two prevailing aspects Dr. Mitrasinovic is interested in are: (1) the reaction pathways for biologically important radicals, such as peroxyl radicals, tryptophan radicals, and tyrosyl radicals, as well as the effects of the biological environment on their mechanisms and (2) detailed insight into very complex DNA-DNA, DNA-protein, and DNA-peptide cross-links. His expertise is the development of the complete biochemical reaction mechanisms leading to all sorts of cross-links between physically realistic model compounds. Powerful computational techniques, such as density functional theory methods, are employed to investigate the feasibility of each reaction step, taking into account kinetic and thermodynamic arguments as well as solvent-induced effects. By this approach, detailed insights into the role of hydrogen-bonding interactions in various hydrogen-transfer reaction steps are possible. The consistent use of the contact spin density distribution, having a profound impact on hyperfine interactions observed in important free bioradicals, is a great virtue of Dr. Mitrasinovic’s work, and thereby advanced biochemical reactions become fully rationalized. As a consequence, assignment of the spectra to specific radicals is to be placed on a more rigorous basis through comparisons of accurate theoretical calculations and experimental data.

Electron Transfer, Hydrogen and Peptide Bonds

It is well known that peptide bridges play a key role in long-range electron-transfer reactions taking place in proteins. The role of the peptide spacers is not only to separate the donor and the acceptor, but also to assist by way of electronic states the actual electron tunneling between the donor and acceptor electronic states. The question to which Dr. Mitrasinovic seeks the answer is how distance increase and concomitant intramolecular hydrogen bonds influence the electron tunneling for a whole family of structurally well-defined peptide systems.