Have You Heard of the Protein-Folding Problem?

I had planned to highlight the top ten scientific achievements in 2021 on this New Year’s Day, but one achievement stands out so significantly that I’m devoting my blog to the solution of the protein-folding problem.

The human body has around 100 million proteins, which govern much of how our bodies work. Some transport messages between cells; some break down or create molecules like fats, proteins and sugars; some control blood pressure; some replicate DNA; some respond to stimuli, some provide cell structure, and others have different roles. They are the body’s workforce. The shape of the protein molecule determines its job. They are made up of chains of amino acids, which uniquely determine the shape. Biologists have long lusted over the ability to predict shapes from the chains involved, labeling it the folding problem. I had to dig to understand why they used the word folding. The best analogy I could find is to view the given amino acids as ribs on Christmas ribbons. Folding becomes similar to taking a blade of a scissors and dragging it along the ribbon in several places. You end up with those lovely curls, shaped like a helix. Somehow the chain of amino acids dictates where the curls occur.  However, the number of possible shapes from a given chain of amino acids, the order and the number of each, is so large that programming a computer to test all shapes to compare with the given protein is infeasible.

One of the reasons that understanding the relation between the chain and the corresponding protein molecule is that misfolding is responsible for some diseases such as alzheimers, parkinsons, and diabetes. Scientists have been able to associate the shape to function only in a small fraction of the 100 million protein molecules, but using AI, Alphafold, a division of DeepMind, a British company acquired by Google, they can determine the shape from the amino acid chain. Understanding the structure of proteins is said to have tremendous consequences  for designing drugs, controlling disease, designing enzymes to break down plastic, finding ways to capture carbon, and “?.” Further, AlphaFold is making use of their discovery freely available for such purposes.

Let’s view this as hope for a better New Year and an ultimate cure for future pandemics.

PS So far so good for the James Webb telescope’s journey to the far side of the moon.