Christopher Chapman <cchapman at ag.arizona.edu> writes:
> 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.
There's a ton of it out there, even books.
> 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.
Find a nice general biochemistry text, Zubay or Stryer will work fine.
> 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?
This is true. They are called chaperonins and they've been studied for
at least the past 25 years. Have fun reviewing that literature - heh,
i almost did one of my qualifying exams on them...
> Thirdly, I was wondering if proteins _always_ refold spontaneously in
> solution to their native conformations after being unfolded.
No. you might as well shoot yourself in the foot if you're going to
say 'always' in science. some proteins can do this, some need help,
some just won't refold.
> 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?
I strongly suggest you first read some biochemistry; either that or
take a biochem class. Nothing can substitute for the basics.
Additionally, you should point your browser to
http://www4.ncbi.nlm.nih.gov/Entrez/medline.html and do some
literature searches. a cursor search for 'protein and folding'
revealed more than 8000 matches. adding the word 'problem' brings this
down to 214 matches.
have fun...
-pjf
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