siegeljb Staff Lv 1
As environmental impact becomes an increasing concern for chemical manufacturing, the idea of using enzymes in environmentally friendly conditions to catalyze chemical transformations instead of traditional chemistry is becoming increasingly important. Unfortunately, naturally occurring enzymes only catalyze a subset of the reactions that are readily available to the synthetic chemist. Therefore engineering enzymes to catalyze novel chemical reactions is an area of great interest. To address this we are using the computational tool ROSETTA to engineer an enzyme capable of catalyzing one such reaction: an intermolecular, stereospecific Diels-Alder reaction. While no clear examples of this reaction have been shown to occur in nature, it is one of the corner stone reactions used by synthetic chemists to form carbon-carbon bonds and received a Nobel prize in 1950 (http://en.wikipedia.org/wiki/Diels%E2%80%93Alder_reaction). While popular with synthetic chemists, this reaction often falters due to the large number of different products that can be formed when bringing two molecules together. With an enzyme we can control the way the two molecules come together during the reaction, therefore we will be able to catalyze the formation of a single product. We hope that this novel enzyme and more like it will introduce a new class of environmentally friendly chemical reactions available to the biochemist’s tool bench and lead to the creation of new drugs, commodity chemicals, and more!
The “Cover the Ligand” Puzzle is one of the Diels-Alder enzymes we are currently engineering. Unfortunately only half of the ligand is covered making it so our initial design is a weak binder. With your help we would like to increase the size of the loops surrounding the ligand, allowing additional amino acids to touch the ligand, which should result in an increase of this enzymes catalytic efficiency.
Your designs will be ranked based on score and number of additional contacts made to the ligand. The most promising of your designs will then be synthesized and experimentally tested in the Baker lab. We look forward to seeing all of the exciting new solutions you come up with!
