[Nescafe]

Hi,

Isnt the folded protein more ordered than the unfolded? How come protein folding is said to be entropically favorable?

I understand the meanings of entropy and enthalpy but cant seem to wrap my head around why it is so. My only guess is that by folding there is a deduction in the exposed hydrophobic surface area and as a result of this folding and minimization of the exposed hydrophobic surface the water molecules surrounding the unfolded chain are liberated (entropically favorable event).

Anyways, now I feel like I might be half right after I wrote that =)

Many thanks,

Nescafe.

[Yggdrasil]

Where did you hear this?  In general, protein folding is enthalpically favorable (ΔH < 0) but entropically unfavorable (ΔS < 0).  This is why proteins will unfold when heated.

You are correct that hiding the hydrophobic surfaces in the interior of the protein is entropically favorable (the hydrophobic effect), but the gain in entropy from the hydrophobic effect does not counteract the loss of conformational entropy that comes from folding the polypeptide chain into a particular configuration.

[Nescafe]

Where did you hear this?  In general, protein folding is enthalpically favorable (ΔH < 0) but entropically unfavorable (ΔS < 0).  This is why proteins will unfold when heated.

You are correct that hiding the hydrophobic surfaces in the interior of the protein is entropically favorable (the hydrophobic effect), but the gain in entropy from the hydrophobic effect does not counteract the loss of conformational entropy that comes from folding the polypeptide chain into a particular configuration.

Hi it is on page 194 of Modern Physical Organic Chemistry by Anslyn. I find it to be quite strange as well but I always tend to get puzzled in this area of Med Chem as there are so many gray areas and people seem to have evidence to prove eachother wrong :S But I agree with your explanation.

Nescafe.

[Babcock_Hall]

Among general biochemistry textbooks, the fourth edition of Matthews, Van Holde, etc. have the most coverage of which I am aware, pp. 196-200.  I agree with Yggdrasil that entropy is usually always unfavorable overall, despite the contribution from the hydrophobic effect.