protein folding

kresten no-sp at m.org
Mon May 21 06:28:20 EST 2001



> Your question assumes that (1) a potential energy function can be
described
> and that (2) the "normal" or functional conformation of a protein is one
in
> which the potential energy is at a global minimum. But neither of these is
a
> valid assumption.

This I don't get.
(1) Why shouldn't we be able to "describe" the potential energy function, at
least for some subspace of the conformational space.

(2) I have argued before that we may never know for sure whether proteins
attain their global minimum (without breaking bonds!) in their native fold.
However, in almost every known case there is no reason whatsoever to assume
that the Anfinsen hypothesis (proteins fold to their energy minimum) is not
true. If you think this isn't the case, please explain why.

> In particular, (2) is biologically meaningless, because a protein in its
> global minimum would not be capable of assuming different conformations
> without an external input of energy.

Take a simple organic molecule and look at it's rotational or vibrational
spectrum. It vibrates. It rotates. However, it's average structure is most
probably the global energy minimum. However, where there is life there is
always thermal energy available. In other cases enzymes may require
additional energy e.g. from ATP hydrolysis in order to carry out their
function.

> The proper functioning of most or all
> enzymes, for example, requires that they alternate between different
> 3-dimensional conformations. In other words, enzymes must exist in
metastable
> local energy minima.

How would such a mechanism work? What would make these proteins change
between their different local minima. If these proteins never get any
external energy as you suggest why do they not end up in a global minimum
where they - according to your statement - would be inactive. I think what
you are suggesting is a perpetuum mobile. Please correct me if I
misunderstand you.

> The old saying applies to enzymes, I think, just as much as to living
> organisms: "A system at its global energy minimum is dead."

Obviously we as an organism is not at a global minimum. Also, of course an
enzyme at its global minimum would (at least) get hydrolysed to amino acids.


Kresten





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