AlphaFold is a useful tool but it's unsatisfying from a physical chemistry perspective. It doesn't give much if any insight in to the mechanisms of folding, an

AlphaFold is a useful tool but it's unsatisfying from a physical chemistry perspective. It doesn't give much if any insight in to the mechanisms of folding, and is of very limited value in designing novel proteins with industrial applications, and in protein prediction for membrane-spanning proteins, extremophilic microbe proteins, etc. Thus things like folding kinetics of transition states and intermediates, remain poorly understood through such statistical models, because they do not explicitly incorporate physical laws governing the protein system, such as electrostatic interactions, solvation effects, or entropy-driven conformational changes. In particular, environmental effects are neglected - there's no modeling of the native solvated environment, where water molecules, ions, and temperature directly affect the protein’s conformational stability. This is critical when it comes to designing a novel protein with catalytic activity that's stable under conditions like high salt, high temperature etc. As far as Nobel Prizes, it was already understood in the field two decades ago that no single person or small group was going to have an Einstein moment and 'solve protein folding', it's just too complicated. This award is questionable and the marketing effort involved by the relevant actors has been rather misleading - for one of the worst examples of this see: https://www.scientificamerican.com/article/one-of-the-biggest-problems-in-biology-has-finally-been-solved/ https://www.scientificamerican.com/article/one-of-the-bigges... For a more judicious explanation of why the claim that protein folding has been solved isn't really true: "The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins" (June 2024) https://www.nature.com/articles/s41589-024-01638-w https://www.nature.com/articles/s41589-024-01638-w