What is AlphaFold2? One good use of artificial intelligence and the Nobel Prize in Chemistry 2024

Scientists have struggled for more than 50 years to solve what was called “the protein folding problem.” Proteins are complicated, and elucidating their structure used to take decades and even longer to understand how they work. That is still true, but AI has been helpful.

Why is protein folding important? We may think DNA is complicated, but it’s not as complicated as a protein. DNA, whatever its origin and sequence, folds in space in a similar manner, as shown by Watson, Crick and Wilkins (1962 Nobel Prize in Physiology or Medicine, Rosalind Franklin had already died). Remember the double helix? Now look at those pretty models of proteins you see on Wikipedia. Not two are the same. Proteins begin as strings of amino acids before twisting and folding into three-dimensional shapes that define what they can and can’t do. Wrong folding, and there goes the binding to a specific receptor or the catalysis of a chemical reaction. Activity  is all in the folding! This is why protein design and purification is a craft, as I learned for decades in the lab.

Each protein is different. They have to be able to do their job, which can be incredibly specific. Think about the effect of a change in a single amino acid. The protein may have no activity depending on where the amino acid change is. This is the cause of many genetic illnesses and also of many cancers. When a protein that is in charge of controlling one of the many processes that lead to cell division changes, disaster ensues.

What about this Nobel Prize in Chemistry? Biochemists have used AlphaFold 2 to speed up the discovery of medicines, and it could also lead to new biological tools such as enzymes that efficiently break down plastic bottles and convert them into materials that are easily reused and recycled. Three scientists received this years’ Nobel for computational chemistry for protein design.

What benefits will it bring to us? We will gain a better understanding of how things work in the cell. Eventually, we will find ways to control viruses and bacteria and cure diverse illnesses. We will modify proteins so that plastics can be broken down. The same goes for “forever chemicals.” Nothing is forever, but some chemicals may require new enzymes to break them.

So, once again, science is bringing good news. As always, it is a reminder not to play with the unknown.

Hannah