Here is maybe a helpful analogy for the challenges behind protein folding. The 5HT2A receptor is comprised of 471 amino acids. Proteins fold based on interact

Here is maybe a helpful analogy for the challenges behind protein folding. The 5HT2A receptor is comprised of 471 amino acids. Proteins fold based on interaction between each of those amino acids, plus the external environment (plus post-translational modification). So imagine a length of string with 471 magnets attached to it with different magnetic field strength (ranging from weak to strong). Now imagine it floating in space - how would the string fold upon itself? Now imagine different segments of the string have different stiffness - some are super flexible, others are rigid. Difficult to predict how it might fold? Oh yeah! Now imagine the string not in space, but in a solution of water with a number of other magnets floating in it (the cytoplasm within the cell and external environment outside the cell). Oh, and also imbedded in a wall with magnets in it as well (the cell membrane). Now how does it fold? Ok, now we think we have a good approximation of the structure just based off of various pieces of data. But wait! Other proteins are also embedded in the cell wall - all with their own structures and selection of weak and strong magnets, stiff and flexible segments interact with the receptor! Oh, and not all receptors have the same external environment - that can differ based on another laundry list of factors. Yeah, that's another layer of complexity. Then add on top that the external environment (inside the cell on one side, outside the cell on the other) has a ton of water, but also dissolved ions like Na+, K+, Cl-, plus a bunch of other proteins with their own "magnets" and "stiff and flexible segments". These outside molecules will bind and disassociate from the receptor on a constant basis, ever so tweaking the shape. Oh crap. Of course AI has a good starting point - we can get x-ray crystal structures of the receptor and identify the position of atoms. But wait! That's in a crystal, not a human body! So that structure is likely incorrect in several ways. We also have other analytical techniques that can give clues to the structure in a solution that more closely mimics what's inside the body, so we can at least tell when the x-ray structure is just wrong (at least in some places). That should give people an idea just how complex protein folding is. AI is good at taking all known "rules" about protein folding (and molecule interactions with the protein) to improve the predictions. But we're still far off from truly understanding all the factors in play.