Project 7 Jun.-Prof. Stefan Günther
Fragment–based in silico screening of cofactor binding sites: a bioinformatic approach to identifying new biomimetics
Nicotinamide adenine dinucleotide (NAD) participates in a diverse range of cellular processes, including hydride transfer in enzymatic reactions, signal transduction and DNA repair. These processes and the related proteins are involved in various diseases, thus molecules that affect NAD-binding proteins have a high therapeutic potential.
- Structural classification of NAD-binding proteins
- Identification of putative drug targets. Classified binding proteins will be scrutinized for candidates that are specific for non–human organisms, particularly microorganisms
- Preparation of a library of biomimetics
- Identification of specific NAD biomimetics
- Experimental validation of candidate molecules
Figure 1: Fragment AJ1 occupying the binding pocket of the cofactor NAD in human muscle lactate dehydrogenase (LADH). The fragment binds specifically to the adenine–moiety binding region. AJ1 is shown in stick representation (PDB-ID: 4AJ1, Ward et al.. The structure of NAD co-crystallized with LADH was superimposed in wire representation (PDB-ID: 1I10).
Jun.-Prof. Dr. Stefan Günther
Institute of Pharmaceutical Sciences
Phone: +49 (0) 761 203-4871
Fax: +49 (0) 761 203-97-769