Protein folding thermodynamics

[jhirlo]

My textbook’s explanation for spontaneous renaturation of defolded protein is this:

“Although in defolded state protein has grater entropy, greater degree of disorder, it folds into original conformation (lower entropy), and this seems to be in collision with the II law of thermodynamics. But by refolding molecules of water surrounding him increase its own entropy by forming maximum number of hydrogen bonds (they’re squeezing, pushing in hydrophobic regions from protein surface inside of protein, allowing hydrophilic regions to come out to surface to form H-bonds with water), so net change in entropy of solute and protein is than increase of entropy, and process is spontaneous.”

Thing that I disagree in this that by forming hydrogen bonds water is increasing its own entropy, how can this be true ?
By forming maximum number of (or generally forming) hydrogen bonds water increases its order, by organizing own molecules in ordered fashion dictated by hydrogen bonds. Than how can this H-bond forming could be S increasing?

Please help.
Regards.

p.s. Sorry for posting in two rooms, but because of type of this massage bio/physics, I think that’s the way I’ll get best (or any:)) answers

[nautica]

There is more to deal with in a system than entropy alone. Look at the Gibbs free energy equation.

Besides, the second law was never intended to deal with what happens inside a system only what happens to the system as a whole. It states that the NET movement must be static or toward entropy.

This sounds like an argument from a creationist.

Nautica

[Another God]

There is more to protein folding than just entropy states. If protein folding was spontaneous, then allowing a cooked egg to cool down again would have the egg turn back into a runny state as the proteins all renatured.

It has a lot to do with chaperone proteins assisting the process and other stuff which I can't think of right now off the top of my head.

[jhirlo]

OK, I agree with your remarks. But those aren’t answers to my question.

Of course not all denaturized proteins will be able to refold spontaneously, some will, and some will use chaperones, but some will do this without any help (you must know about Anfinsen’s classical experiments with denaturized RNase, that in more than 90% cases folds again to active state without any help).

dG = dH - TdS (and consider protein with surrounding water observed system)

But how do you explain spontaneous refolding ?
Only way spontaneous refolding could happen is decrease of free energy of the system. And it is obvious how this can be done considering this equation.
You have to increase S or have negative dH. What mechanism you propose for this change?

[amc]

Think about it in terms of surface area. A folded protein has less surface area. We know that water forms an ordered solvation shell around the protein. So if the ordered shell has less molecules in it (as it would for a folded protein, since a folded protein has less surface area than an unfolded one) then we can assume the water gains entropy (ie, more water molecules are in the bulk, which is less ordered).

[disparu]

Only way spontaneous refolding could happen is decrease of free energy of the system. And it is obvious how this can be done considering this equation.
You have to increase S or have negative dH. What mechanism you propose for this change?

Your remark here is absolutely correct, the protein must minimizes its structural free energy.
Enthalpy is just important as entropy in this respect.

The simplest microscopic (i.e. statistical mechanical) description of protein folding free energy is probably the so-called HP model. I found a technical summary here for example.
http://sites.google.com/site/fnbraun/miscellany/elisp-bioinformatics-example/simplest-hp-model

The explanation given by the textbook you mentioned earlier seems a bit confusing.
Have you checked out the textbook called 'Molecular Driving Forces' by Ken A. Dill?
That is really clear...