Delineating protein kinase design principles using evolutionary-systems approaches
Protein kinases are exquisitely designed molecular machines that display remarkable diversity and complexity in their mechanisms of action. We are mining the wealth of evolutionary information embedded in protein kinase sequences from diverse organisms to obtain an in-depth understanding of the evolutionary rules that govern the structure and regulation of these proteins. Important goals are to quantify the sequence similarities and differences between functionally divergent kinases using statistical and computational approaches, and to experimentally test the role of evolutionarily constrained motifs using biochemical and biophysical techniques. We are also conceptualizing protein kinase knowledge in the form of ontology to facilitate systems level analysis of protein kinase data.