AI has designed bacteria-killing proteins from scratch – and they work

AI was tasked with creating a protein with antimicrobial properties.The researchers then created a subset of proteins and found that some worked

To Carmela Padavich-Callaghan

The AI-designed antibacterial protein was tested in the wild and shown to work. Ultimately, the same approach could be used to create new drugs.

Proteins are made up of chains of amino acids. The sequence of these acids determines the protein’s shape and function.

Ali Madani and his colleagues at Salesforce Research in California have used AI to design millions of new proteins and create small samples of them to test if they work.

AI called ProGen works similarly to AI that can generate text. ProGen learned how to generate new proteins by learning the “grammar” of how amino acids combine from 280 million existing proteins. Instead of teams choosing topics and styles for the AI ​​to write about, researchers can specify groups of similar proteins for the AI ​​to focus on.

Madani says he has programmed checks into the AI’s process to ensure it doesn’t produce “meaningless” amino acids, but to actually test it, we need to know how the proposed molecule behaves in cells. I wanted to see if it works for Of the 100 they physically created, 66 participate in chemical reactions similar to the natural proteins that destroy bacteria in egg whites and saliva, suggesting that they can also kill bacteria.

Focusing on the five proteins whose responses were the strongest, they Escherichia coli Bacteria and Saw 2 destroy it very well.

The researchers then imaged them with X-rays. Even though their amino acid sequences differed from existing proteins by up to 30%, the shapes they saw were nearly identical to naturally occurring proteins. James Fraser, who was part of the team at the University of California, San Francisco, said it wasn’t clear from the outset whether an AI could alter amino acid sequences so much and still figure out how to reproduce the correct shape. increase.

“It’s like a ‘looks like a duck, quacks like a duck’ situation, and even X-rays confirmed it walked like a duck,” says Fraser. He was surprised to find a well-functioning protein in the first relatively small fraction of all his ProGen-produced proteins they tested.

A similar process could be used to create new test molecules for drug development, but they still need to be tested in the lab, which takes time, says Madani.