Science: AI solved the protein folding problem!!

One way that researchers discover new drugs and how living thing function is by finding out the precise 3-dimensional structure of proteins. In biomedical research, that information is used to find new treatments or prevent specific diseases or conditions. In my days in the lab (1970s-1980s), it was slow as cold molasses. The protein had to be crystallized into a big enough crystal for X-ray crystallography (later replaced by cryo-electron microscopy) to determine its precise structure. It was costly, tedious and required huge effort for each protein.

Then along came an AI (artificial intelligence) program called AlphaFold (see 2 minute video below). 

Although I missed this somehow (bad Germaine, bad, bad Germaine), in 2022 the AI AlphaFold program was able to take the amino acid sequence of any protein (presumably along with information about post-translational modifications, if any) and draw a precise 3-D structure for the protein. This is a big deal. Using a lock and key analogy, a 2022 CNet article comments about why knowing precise protein structure is important:

Google's DeepMind AI Predicts 3D Structure of 

Nearly Every Protein Known to Science

At last, the decades-old protein folding problem may finally be put to rest

"More than 500,000 researchers and biologists have used the database to view over 2 million structures," Hassabis said. "And these predictive structures have helped scientists make brilliant new discoveries."

In April, for instance, Yale University scientists called on AlphaFold's database to aid in their goal of developing a new, highly effective Malaria vaccine. And in July of last year, University of Portsmouth scientists used the system to engineer enzymes that will fight against single-use plastic pollution.

Structure of vitellogenin, an egg yolk protein

So, why do so many scientific advancements depend on this treasure chest of 3D protein modeling? Let's explain.

Suppose you're trying to make a key that fits perfectly into a lock. But you have no way of viewing the structure of that lock. All you know is this lock exists, some data about its materials, and maybe numerical information on how big each ridge is and sort of where those ridges ought to be.

Developing this key wouldn't be impossible, maybe, but it'd be quite difficult. Keys have to be precise, otherwise they don't work. Therefore, before you get started, you'd probably try your best to model a few different mock locks with whatever info you do have so you can make your key.

In this analogy, the lock is a protein and the key is a small molecule that binds to this protein.

For scientists, whether they're doctors trying to craft novel medications or botanists dissecting plant anatomy to make fertilizers, interplay between certain molecules and proteins is crucial.

With medications, for instance, the specific way a molecule in a drug binds to a protein could be the breaking point for whether it works. This interaction gets complicated because even though proteins are just strings of amino acids, they're not straight or flat. They inevitably fold, bend and sometimes tangle around themselves, like headphone wires in your pocket.

In fact, a protein's unique folds dictate how it functions — and even the slightest of folding mistakes in the human body can lead to disease.

Structure of an antibody

What AlphaFold had done as of July 2022

By Germaine: The one with bad information scanning protocols