Researchers at the Howard Hughes Medical Institute, with the help of people all over the world donating some of their computer processing power through the Rosetta@Home project, managed to create two brand new enzymes never seen in nature.
For the enzyme design project, Baker’s team [David Baker, HHMI Investigator and Professor of Biochemistry at the University of Washington, Seattle –ed.], led by senior fellows Daniela Rothlesberger and Eric Althoff and graduate students Lin Jiang and Alex Zanghellini, designed active sites they thought would speed up the chemical reactions. They then used the Rosetta@home network to find amino acid sequences that would fold to produce those active sites. After that step, they created actual genes encoding those amino acid sequences and inserted them into bacteria to see if the proteins they produced speeded up their reactions.
According to Baker, the enzymes worked, though not as well as those found in nature. “Rather than speeding up the rates of reaction a trillion-fold, we’re only getting on the order of 100,000-fold rate enhancements,” he said. “There is clearly something we’re missing, and very important to [our research] is trying to figure out what that is.”
To help, Baker’s Israeli collaborators, Dan Tawfik and Olga Khersonsky (co-authors of the paper that appears in Nature), took one of the enzymes and forced it to evolve. Working in a test tube, the pair created thousands of versions of the enzyme with random mutations. By chance, some of these mutations sped their enzyme up. According to Baker, several rounds of “directed evolution” improved the enzyme’s speed 200-fold, and analyzing the changes will help the team fine tune their computer models for future projects.
Press release: Building Enzymes from Scratch
Abstract: Prediction and Design of Macromolecular Structures and Interactions…