Affiliation: Schering AG, Research Center Europe, Structural Biology, 13342 Berlin, Germany.
Protein kinases are major drug targets in pharmaceutical companies. A deep understanding of the features of the ATP binding niche is of utmost importance for the assessment of drugability and selectivity. This article focuses on recent developments in experimental and theoretical methods relating to structural aspects of drugability and selectivity. Predicting drugability is enabled by a detailed analysis of the structural characteristics of binding sites. Our in-house approach for the assessment of drugability and selectivity involves an interaction profile analysis (IPA) and is derived from available structural information of protein kinases. IPA as well as other methods introduced in this article can assist in explaining observed selectivity pattern. For a reliable prediction of selectivity of a protein it is necessary to enrich the currently available database by structural and affinity data.