David Baker: Why do proteins matter?

In this edition of Titans of Science, Chris Smith chats to David Baker, the Nobel Prize winner who used AI to design custom proteins...

Chris - David Baker was born to two parents who were themselves, both scientists, in Seattle on the 6th of October, 1962. He attended Garfield High School in the city before he read biology at Harvard University. On graduation, he then began working on how proteins are transported around cells. Later, he would go on to pioneer methods to design proteins and predict their three dimensional structures, and that helped to earn him a share of the 2024 Nobel Prize in chemistry. David co-founded several biotechnology companies and he was included in Time Magazines inaugural list of the 100 most influential people in health. He's now the director of the University of Washington's Institute for Protein Design. Welcome to the show, David, and congratulations on your Nobel Prize. How did your interest in science get started?

David - Well, perhaps surprisingly, I really became interested in science relatively late. I'm not one of those people who's fascinated by science from an early age. In fact, when I got to the university, I initially declared my major to be social studies, and later I got interested in philosophy. And it was really not until my last year of college that I decided to switch to science and focus on biology.

Chris - But proteins, I mean, I remember my biology teacher at school. I wasn't very old obsessing about proteins. I really didn't get what all the fuss was about. Why did they matter to you? What drew you into that and why do they matter to anybody?

David - Well, in fact, at the time I was in University, I had no idea what proteins were either until I took a biology class. And it seemed interesting to me, but it wasn't until quite a few years later that I really started becoming obsessed. And I'll tell you why. In nature, you know, biological organisms, animals, humans do all kinds of really, really amazing things. And if you look in detail how those things are accomplished, at the heart of everything are proteins. So there are specialised proteins that mediate the electric currents through our brains while we're thinking and talking. There are proteins that allow us to move around. There are proteins that enable plants to capture solar energy from the sun and use it to make molecules. Basically everything that goes on in biology is done by proteins. So the way that biology works is there are all these different jobs, thousands and thousands of jobs in any organism. And for each job there's a specific protein. So you can kind of think of proteins as the miniature machines, which do all the important things in life.

Chris - And what's their structure? How would I recognise one?

David - You wouldn't recognise one if you saw it because they're extremely small. They're just one nanometre across, which means that you need a trillion of them to get to a metre. But each protein has a very well-defined shape. That's one of the really kind of miraculous things about proteins. If you think about the machines that we're used to encountering in real life, each machine has a very defined shape, which is really important for it to do its job. Like a car has wheels so it can roll, and it's got an interior compartment you can get into. And in the same way every protein has a very defined shape. And those shapes are really what lets the proteins do what they do.

Chris - How do they come by that shape though?

David - Proteins carry out all the work in our bodies and all living things. Like I said, the instructions for making proteins are in our genomes in the DNA. And so the DNA in our genomes specifies what the chemical structure of each protein is. That is what the sequence of amino acids is going to be. Proteins are made out of amino acids. There are 20 different types of amino acids, and a protein is a linear chain of about 100 to 500 amino acids. And the sequence of amino acids of a protein completely determines what its shape is. And that sequence, as I said, is specified in the genes in our genomes.

Chris - And those amino acids are all different chemically. So they can have different shapes, different structures, different sizes, different electrical behaviours. And so that means depending upon which ones you slot in, it's a bit like building a wall with different shaped bricks. You are going to get a different shaped wall or a different coloured wall or a wall with interesting properties if you put different amino acids into it.

David - Yes, that's a very good analogy. It's kind of like having a universal building block kit, kind of like a child's construction toy where you can basically make any shape by having the right combination of amino acids. And it's not just the shape, the machine also has to interact with whatever it's operating on in the right way. So by having certain types of amino acids on the surface of a protein that will enable it to interact with other proteins or with DNA and carry out the job it's meant to do in biology.