Most proteins don't fold to their global energy minimum- they fold to a collection of kinetically accessible states. Many proteins fail to reach the global minimum because of intermediate barriers from states that are easily reached from the unfolded state.
Attempting to predict structures using mechanism that simulate the physical folding process waste immense amount of energy and time sampling very uninteresting areas of space.
You don't want to use a supercomputer to simulate folding; it can be done with a large collection of embarassingly parallel machines much more cheaply and effectively. I proposed a number of approaches on supercomputers and was repeatedly told no because the codes didn't scale to the full supercomputer, and supercomputers are designed and built for codes that scale really well on non-embarassingly parallel problems. This is the reason I left academia for google- to use their idle cycles to simulate folding (and do protein design, which also works best using embarassingly parallel processing).
As far as I can tell, only extremely small and simple proteins (like ribonuclease) fold to somewhere close to their global energy minimum.
Except, you know, if you're trying to understand the physical folding process...
There are lots of enhanced sampling methods out there that get at the physical folding process without running just vanilla molecular dynamics trajectories.
Attempting to predict structures using mechanism that simulate the physical folding process waste immense amount of energy and time sampling very uninteresting areas of space.
You don't want to use a supercomputer to simulate folding; it can be done with a large collection of embarassingly parallel machines much more cheaply and effectively. I proposed a number of approaches on supercomputers and was repeatedly told no because the codes didn't scale to the full supercomputer, and supercomputers are designed and built for codes that scale really well on non-embarassingly parallel problems. This is the reason I left academia for google- to use their idle cycles to simulate folding (and do protein design, which also works best using embarassingly parallel processing).
As far as I can tell, only extremely small and simple proteins (like ribonuclease) fold to somewhere close to their global energy minimum.