Since about 2000, a major focus of our research has been the selection and engineering of a variety of proteins and enzyme catalysts for new, improved or altered biophysical properties such as their folded structure, their thermostability, their binding specificity and affinity, and (in the case of enzymes) their catalytic abilities and substrate specificity.
In 2002, we carried out what was (for us) a seminal experiment in which we created a fully active, chimeric homing endonuclease capable of recognizing and cleaving a complementary chimeric target site. As part of that project, we discovered that computational algorithms being developed David Baker’s laboratory at the UW could be successfully applied to such problems, by repacking a protein interface and creating a novel domain packing architecture. Subsequently, we (the Baker lab and ourselves in various collaborative mixtures) have used similar algorithms with great success to design a novel protein fold, novel protein-protein heterodimer association specificity, and enzyme catalysts with new activities, specificities, and thermostabilities.
We are currently involved in an ongoing set of collaborations with: