I am considering working on the protein folding problem from the
theoretical side for my dissertation topic, and am looking for some very
specific information.
First of all, I would like a pointer to some material that outlines how
proteins are formed within the cell itself, from DNA transcription to
how the ribosomes construct them.
Second, I have heard that there are molecules in solution that actually
may guide the folding process, is this true? Any studies you could
point me to?
Thirdly, I was wondering if proteins _always_ refold spontaneously in
solution to their native conformations after being unfolded. Are their
folded states natural and spontaneous, or is it dependant on the process
that creates them? Again, are there any studies that you could point me
to? I have seen many studies that show that predicted tertiary
structures are of lesser energy (higher entropy) according to the
fitness functions being used than the native structure would have. Is
this because the fitness functions are not accurate or because native
structures do not really lie in the absolute minimum of the potential
energy surface (i.e. - the lowest energy point in conformation state).
Is it possible that the structures are guided somehow to a local
minimum, rather than folding independantly to the global minimum? Has
anyone done an extensive simulation to prove that the native structures
are indeed at the global minimum potential energy point in conformation
space?
Finally, If there is anyone with protein folding knowledge who wouldn't
mind making themselves available to me to consult from time to time, I
would appreciate it. I won't require much of your time, but I am an
engineer and my expertise is in the physics, computational, and applied
side of things. I am not a molecular biologists, and I feel that many
of the attempts to apply computational chemistry to this problem have
ignored the complexity of the cellular system and how it affects the
process of folding. Thanks for any reply.
Christopher Chapman
cchapman at ag.arizona.edu
The Department of Ag. & Biosystems Engineering
The University of Arizona
