AI makes proteins speed up chemical reactions

For the first time, scientists have used machine learning to create brand new enzymes, which are proteins that speed up chemical reactions. This is an important step in the field of protein design, as new enzymes could have many uses across medicine and industrial manufacturing.

“Living organisms are amazing chemists. Instead of relying on toxic compounds or extreme heat, they use enzymes to break down or build up whatever they need under gentle conditions. New enzymes could make chemicals and biofuels in -renewal under control,” said senior author David Baker, a professor of biochemistry at the University of Washington School of Medicine and recipient of the 2021 Breakthrough Prize in Life Sciences.

As reported February, 22 in the magazine nature, a team based in the Institute for Protein Design at UW Medicine devised machine learning algorithms that can create light-emitting enzymes called luciferases. Laboratory testing confirmed that the new enzymes can recognize specific chemicals and emit light very efficiently. This project was led by two postdoctoral students in the Baker Lab, Andy Hsien-Wei Yeh and Christoffer Norn.

The IS nature paper entitled “De novo design of luciferases using deep learning.”

To create new luciferase enzymes, the team first selected chemicals called luciferins that they wanted the proteins to act on. They then used software to generate thousands of protein structures that could react with those chemicals.

During laboratory testing, the researchers identified an effective enzyme, called LuxSit (Let there be light). The enzyme carried out the required chemical reaction. Refinement of the enzyme led to major improvements in performance. An optimized enzyme, called LuxSit-i, generated enough light to be visible to the naked eye. It was found to be brighter than the natural luciferase enzyme found in the glowing sea pansy Renilla reniformis.

“We were able to design very efficient enzymes from scratch on the computer, rather than relying on enzymes found in nature. This means that custom enzymes for almost any chemical reaction could be designed, in principle,” Yeh said.

New enzymes could benefit biotechnology, medicine, environmental remediation and manufacturing. For example, in biotechnology, enzymes can improve biofuel production, food processing and pharmaceutical manufacturing. In medicine, enzymes can serve as therapeutic and diagnostic tools. Enzyme design can improve the environment by breaking down pollutants or cleaning up contaminated sites, and enzymes can also aid in the production of new materials such as biodegradable plastics and adhesives.

This research was led by scientists from the UW School of Medicine and included collaborators at the University of California, Los Angeles.