Hi, computational protein engineer and person who-thinks-biology-can-do-amazing-stuff here.
Just wanted to report that while “Proteins are like Folded Spaghetti Held Together By Static Cling” is obviously incorrect as a matter of fact, I immediately thought it was a pretty good analogy for capturing some critical and often under-appreciated aspects of the functionally important character of proteins. When I read the sentences you’ve quoted him saying about proteins held together by covalent bonds, I (think) I understood what he was pointing at with this and roughly agree. I absolutely did not think he was saying proteins did not contain covalent bonds, but rather that you could imagine an alternative protein-like molecular structure which had all of its key structural and functional characteristics determined by covalent bonds. I believe such a “protein” would, among other things, be predicted to function at a much wider range of temperatures than extant proteins, maintain its structure and function in many different solvents (and probably gas phase?) etc etc.
This analogy is also definitely failing to capture other important characteristics of proteins, some of which the OP mentioned and I agree with.
By the way, if I was forced to say one thing which “held together” proteins (in the sense of “is most responsible for determining the functional characteristics of a polypeptide chain) it would be tough but I might pick something I don’t think anyone has mentioned: hydrophobicity/ hydrophilicity.
Yea, idk. I was thinking of the quotes where you explicitly mentioned Van der Waals forces. Tbc, my preference would be to not be forced to pick a single force