[gabia]

Great points about the energy minimisation issue. Funnily enough, this is actually a problem with de-novo protein design at the moment: the designed proteins are _too_ stable! Compared to natural proteins. Protein are often not static shapes, they are machines that need to be dynamic - in other words what you said, they do not live at some deep global optimum.

[eru]

Interesting point!

> [...] in other words what you said, they do not live at some deep global optimum.

I think what you said only depends on the minimum being relatively flat (instead of deep); but it doesn't matter whether it's global or local.

[exmadscientist]

> I think what you said only depends on the minimum being relatively flat (instead of deep); but it doesn't matter whether it's global or local

No. There is no such thing as a "global minimum" energy conformation, because the conditions vary wildly. Many protein structure changes are brought about by changes in the local chemical potentials and even electric fields. This is not something you can get a good grip on by thinking in terms of "flat minima".