maglor at bsac.uchc.edu writes:
(stuff deleted)
I agree with your points about the folding of different proteins possibly
occuring by different mechanisms (different values of rate constants etc).
The aim of my contributions to this devate have was to try and counter the claim
made a long while back that it can be taken as read that _everyone_
thinks that protein folding is thermodynamically controlled, and that
there can be no sensible arguments against this case.
> Finally, for
>predicting 3-D structure I feel that this argument has some but limited bearing.
>Realistically, even the highest energy "kinetically trapped" structures will
>probably have energies and conformations very similar to the GLOBAL MINIMUM.
Similar energies maybe (even completely unfolded states have similar energies
to native states), similar conformations and dynamic properties - who knows?
>Therefore, if we can develop methods for rapidlly predicting these minimum
>energy structures from the amino acid sequence we will gain insight into both
>the kinetic and the thermodynamic aspects of protein folding.
Probably the most important prediction that we need to be able to make
to understand protein FUNCTION, is to know what the NATIVE state is like (from
a knowledge of amino acid sequence).
If the GLOBAL MINIMUM is different to the native state, then there is
going to be a problem for those that don't want to use information pertaining to
natural folding pathways to predict the native state.
_________________________________________________________________________
|| ,_ o Simon M. Brocklehurst,
| / //\, Oxford Centre for Molecular Sciences,
| \>> | Department of Biochemistry, University of Oxford,
| \\, Oxford, UK.
| E-mail: smb at bioch.ox.ac.uk|________________________________________________________________________
