Artificial intelligence has developed proteins that kill bacteria

Artificial intelligence designed antimicrobial proteins that were later tested in real life and shown to work. This approach can be used to create new drugs.

Proteins consist of chains of amino acids. The sequence of these acids determines the shape and function of the protein.

Ali Madani of Profluent, a biotech startup in California, and his colleagues used artificial intelligence to create millions of new proteins, and then created a small sample of them to see if they worked.

Dubbed ProGen, the AI works similarly to artificial intelligences that can generate text.

ProGen learned to make new proteins by learning the grammar of how amino acids fit together to form the 280 million existing proteins. Instead of researchers choosing a topic for the AI to write about, they could specify a group of similar proteins on which it should focus. In this case, they chose a group of proteins with antimicrobial activity.

The researchers programmed checks into the AI’s workflow to ensure it didn’t create amino acid “gibberish,” but they also tested a sample of the proposed AI molecules in real cells. Of the 100 molecules they physically created, 66 participated in chemical reactions similar to those of natural proteins that destroy bacteria in egg whites and saliva. This suggested that the new proteins could also kill bacteria.

The researchers selected five proteins with the most intense reactions and added them to a sample of Escherichia coli bacteria. Two of these proteins killed the bacteria.

The researchers then photographed them using X-rays. Although their amino acid sequences differed by 30% from any existing proteins, their shape was almost identical to natural proteins. James Fraser from the University of California, San Francisco, who was part of the team, says that it wasn’t clear from the start how AI could change the amino acid sequence so much and still create the correct shape.

“It was sort of an ‘it looks like a duck, it quacks like a duck’ situation and X-rays confirmed it also walked like a duck,” Fraser says.

He was surprised to find a well-functioning protein in the first, relatively small fraction of all the ProGen-made proteins they tested.

A similar process could be used to create new test molecules for drug development, although they would still have to be tested in laboratories, which is time-consuming, Madani says.