> "armies of students who routinely spend 4-6 years of their PhD trying to solve a structure of a single protein"
Back in the 1990s, when I worked on structure data, I remember that at least some crystallizations were easy enough they could be done as a rotation project.
> Macromolecular crystallography evolved enormously from the pioneering days, when structures were solved by “wizards” performing all complicated procedures almost by hand. In the current situation crystal structures of large systems can be often solved very effectively by various powerful automatic programs in days or hours, or even minutes. Such progress is to a large extent coupled to the advances in many other fields, such as genetic engineering, computer technology, availability of synchrotron beam lines and many other techniques, creating the highly interdisciplinary science of macromolecular crystallography. Due to this unprecedented success crystallography is often treated as one of the analytical methods and practiced by researchers interested in structures of macromolecules, but not highly competent in the procedures involved in the process of structure determination.
Certainly some proteins are extremely hard to crystallize, and the new single-atom EM work will help a lot. But are there really "armies of students who routinely spend 4-6 years of their PhD trying to solve a structure of a single protein" these days?
I honestly don't know. I'm sure some do. But if so, that army is pretty small compared to the vast numbers who more routinely use crystallography.
I had a friend who solved the structure of 2 or 3 new proteins pretty much by himself his senior year of college. I also had an acquaintance who was a PhD student in the same lab, who said (jokingly) that she hated him because she had spent 5 years on a single protein and got way worse results than he did. I got the sense from talking to them that the process of figuring out how to get a protein to crystallize is basically just trial and error over and over—my friend himself said he basically got very lucky several times in a row (though he is also a brilliant biochemist).
Anyway that anecdote is pretty much the entire sum of my protein crystallography knowledge, but perhaps it explains how your experience and GP's statement can both be true?
Also, one important thing to realize is that AlphaFold was trained largely on proteins that we were able to crystallize. I'd be very curious to see how its performance fares as a function of 'ease of crystallization'.
You aren't wrong. I got caught up making the comparison between structural biologists and taxi drivers being ran out of business by AI, so I ended up exaggerating the work load that's addressed by AlphaFold. I should been more precise.
Back in the 1990s, when I worked on structure data, I remember that at least some crystallizations were easy enough they could be done as a rotation project.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287266/ suggests that life is now a lot easier than the 1990s. Quoting the abstract:
> Macromolecular crystallography evolved enormously from the pioneering days, when structures were solved by “wizards” performing all complicated procedures almost by hand. In the current situation crystal structures of large systems can be often solved very effectively by various powerful automatic programs in days or hours, or even minutes. Such progress is to a large extent coupled to the advances in many other fields, such as genetic engineering, computer technology, availability of synchrotron beam lines and many other techniques, creating the highly interdisciplinary science of macromolecular crystallography. Due to this unprecedented success crystallography is often treated as one of the analytical methods and practiced by researchers interested in structures of macromolecules, but not highly competent in the procedures involved in the process of structure determination.
Certainly some proteins are extremely hard to crystallize, and the new single-atom EM work will help a lot. But are there really "armies of students who routinely spend 4-6 years of their PhD trying to solve a structure of a single protein" these days?
I honestly don't know. I'm sure some do. But if so, that army is pretty small compared to the vast numbers who more routinely use crystallography.