< Back to previous page

Project

Development of a structural database for improved rational kinase drug design.

Protein kinases are an important target for the pharmaceutical research field. In the human genome alone, there are already more than 500 kinases encoded. In order to improve the rational structure based drug design for kinases, we will examine and index all 3D protein kinase domain and store them into a public accessible database. Currently there are over 1500 kinase structures deposited and every year around 100 structures are being added to this number. All of these structures will be optimized on the chemical level, especially the protonation, tautomerisation and bond order of the bound ligands. Using novel developed algorithms, this database will allows researchers to gain structural as well chemical information on a userfriendly and rational level (molecular similartiy 2D and 3D of the bound inhibitors, pharmacophores, interactions with the receptor, 2D-descriptor values, protein conformations, position in the kinome). Furthermore a novel algorithm will be developed which will allow researchers to find structures based on the similarity of the ATP binding pocket to improve homology modelling of kinases or to identify possible targets for cross-reactivity of kinase-inhibitors. In parallel with this research, specific PKD kinase inhibitors will be developed using computer aided drug design. Furthermore a small molecule inhibitors will be designed based on a peptide-peptide interaction (VIRIP) in a collaboration with prof. F. Kirchoff.
Date:1 Nov 2010 →  31 Oct 2011
Keywords:Protein kinase, Proteo-chemo-metrics, Chemo-informatics, Structure based drug design, Molecular modelling, Molecular database
Disciplines:Biochemistry and metabolism, Medical biochemistry and metabolism