3D modeling of macromolecular structures and reactions in the context of genomes

R. R. Gabdoulline, A. Gonzalez and R. C. Wade

EML, Villa-Bosch,
Schloss-Wolfsbrunnenweg 33,
D-69118, Heidelberg
EMBL, Meyerhofstrasse 1,
D-69117,Heidelberg

The 3-dimensional structures of a significant fraction of the proteins encoded by completed genome sequences can be modelled by comparative (homology) modelling techniques. However, modelling results in incomplete models; in particular quaternary structure and cofactors are typically lacking, although these are essential for understanding the mechanism of protein function.

Similarly, in genome analysis, the chemical reactions catalyzed by enzymes are usually described in terms of chemical transformations from the substrate to the product, without detailed information about the function of specific residues in the enzyme that is crucial to understanding its role in a specific genome.

The work described in this poster is aimed at filling this gap between the available information about molecular structures and the detailed models required to understand protein function.

We describe methods and results for

1. definition of active sites and the locations of co-factors and ligands using database annotation and structure-based predictions;
   
   
2. modelling the quaternary structures of proteins and protein-protein interactions;
   
   
3. modelling chemical reactions in their protein structural environments.

The results are demonstrated for the Mycoplasma Pneumoniae genome with particular emphasis on the glycolytic pathway.