The protein folding revolution

Proteins carry out the labor in our cells -- so we really need to know what they do and how they work. The key to proteins is their shape because that dictates their function. They can take many different shapes. Scientists call these folds. Unfolded, a protein is a long string of amino acids. There are 20 different amino acids and each one of them has its own chemical behaviours. When a protein folds up, you get a long tangled piece of spaghetti with all these different chemical functionalities on it It’s not exactly like spaghetti - because its 3D shape evolved over billions of years to do very specific jobs. If you can understand the minute details of the structure of proteins-- not only do you get insights into their function -- you might be able to change that function. So researchers have been trying for many years to solve the protein folding problem: Can we just look at the sequence of amino acids and predict how a protein is going to fold? You could take the amino acid sequence, plug it into a computer, and see if your algorithms are good enough to make sense of how it might fold. You can use X-ray crystallography or other techniques to image a protein structure but that hasn’t been done for very many kinds of proteins. A couple of decades ago folks asked a separate question --could all the genome sequence data- the three billion letters in our genome and the billions in all the other genomes out there - could they scan that code, which is separate from the amino-acid code of proteins, and learn anything about how proteins might fold? The DNA in our genes codes for RNA, which is translated into proteins. So there’s a relationship between the 4-letter DNA code and the 20- letter amino acid sequences of proteins. Because a protein wraps around in many different twists and turns--the 6th amino acid in that chain might end up next to the 18th amino acid. If they end up next to each other, researchers realized there might be an interaction between the pair that is critical to the shape of the protein and therefore its function. If that’s true then a mutation in the DNA that changes one of the amino acids must be accompanied by another mutation to the other member of the pair to preserve the interaction. In essence, they co-evolve. Well, if you can log maybe a hundred or more of those cases of close-by neighbors in 3D space, based on looking at many genome sequences, then you plug that into your folding program. Now that it has all these tight constraints it gives a much better chance of getting a really accurate structure. And it works! The upshot is scientists can fold lots of proteins that they never could before. That’s important because it will give new insights into how those proteins work. Beyond that-researchers have been steadily improving the ability of computers to model the shape of proteins, and this now enables them to design their own proteins---making things never seen before in nature. The most obvious application is medicine. They can target very specific parts of the flu virus with a special built protein-- enabling a vaccine that works across flu strains They've designed proteins that naturally assemble into tiny cages that can deliver different molecules in the body Or, new materials,like engineered surfaces that self assemble could be used in solar cells and electronic devices. you can go in a thousand different directions.

Channel: Science Magazine

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Keywords: Science, Science Magazine, proteins, protein folding, DNA, RNA, medicine, health, materials science

Id: cAJQbSLlonI

Length: 3min 44sec (224 seconds)

Published: Thu Jul 21 2016