VATIS UPDATE Article

A group of researchers from the UW Medicine Institute for Protein Design at the University of Washington, the United States, and the University of Toronto, Canada, recently conducted the largest-scale testing of folding stability for computationally designed proteins. More than 15,000 newly designed small proteins were tested for correlation between folding and function which resulted in significant protein modeling improvements. The new study will speed up progress in designing more stable proteins.

“Computationally designed proteins often fail to form the folded structures that they were designed to have when they are actually tested in the lab,” said lead author Rocklin. Two advanced technologies were used, synthetic DNA and high throughput screening. This new approach, which incorporates advances in DNA synthesis technology, greatly reduced the experimental costs. Researchers tested more than 15,000 newly designed mini-proteins that do not exist in nature, to see whether they form folded structures.

It is a huge step forward since protein design studies in the past have generally examined only about 50-100 different designs. Recent testing led to the design of 2,788 stable protein structures. Small size of these proteins could be advantageous for treating diseases when the drug needs to reach the inside of a cell. “Still, even simple proteins are so complicated that it was important to study thousands of them to learn why they fold,” said Rocklin. The study has been published in the journal Science.