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Re: WSN: hidrophobic/Van der Walls interactions energy... (fwd)
Sender: Rafael Iosef Najmanovich Szeinfeld <szeinfel@snfma1.if.usp.br>
Subject: Re: WSN: hidrophobic/Van der Walls interactions energy...
I don't agree with some of your ideas. You'll find my comments on
it as the appear in your text.
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On Thu, 29 Sep 1994, Bruce Bush wrote:
> There have been many arguments in the field of protein
> folding over whether "polar" or "nonpolar" or "hydrophobic"
> forces cause the folding. Arguments are wasteful when conclusions come
> from *different* definitions. Even worse, many analyses are made
> without *any* clear definition of the terms.
I agree with that.
>
> The breakdown of energy of folding depends completely on how you
> imagine the order of events. I believe therefore that such a breakdown
> of energy into "contributions" is meaningless.
I don't agree with that. The free energy change is due solely to
the balance of the energy contributions of interactions gained and lost.
What deppends on the "order of events" is what interactions can or cannot
be done because any interaction puts a constrain into the portion of
configurational space (or if you preffer the possible future interactions)
available.
>
> What *is* meaningful is to compare the energies of two similar
> processes for two different systems. For example, two versions (mutants)
> of a protein differ at one residue (beta6) which may be nonpolar (Val)
> or polar (Glu). What are the free energies of folding (or aggregation) for the
> two different proteins? If both of the mutants actually fold (or aggregate)
> in nearly the same way -- as verified by crystallography, for example --
> we can ask about the energy contribution of this mutation to the energy
> of folding (or aggregation). But we CANNOT ask about the total energy
> contribution of ALL the polar groups or all the nonpolar groups to the
> energy of folding, because if we changed ALL these groups then the
> protein wouldn't fold!
>
I don't wan't to ask about the total energy contribution of ALL
the polar groups or all the nonpolar groups to the energy of folding.
What I think is almost what you said. First suppose only two monomers
(polar and nonpolar) then change one monomer in such a way that you
create one nonpolar interaction or a polar one. Then tell me what's the
overall free energy change. To think in a world of only to monomers is
equal to average over all polar monomers & kinds of interaction and over
all nonpolar monomers & kinds of interactions.
> At the end I write in more detail about the questions that one can
> and cannot ask about the processes of folding. I hope that these
> imaginary experiments are useful to you in deciding what answer
> you need, and what question to ask.
>
> Bruce_Bush@merck.com
>
> ==================================================================
>
> When a protein folds in water (or two solutes come together, or one solute
> changes shape over a high energy barrier, so that the water has a time
> to "relax" before another change of shape) there is a free-energy change of
> the ENTIRE system (solute molecules plus solvent). There is no single way to
> split this total energy among nonpolar groups, the polar groups, and solvent.
>
As I mentined earlier if you know what have changed in the
structure you may determinate the free energy change due to this
structural change.
> It is possible to define and talk about the forces on various solute
> groups during folding. The force on an atom or group is the gradient
> of the free energy, that is, the change of the *total* free energy
> as the group moves slightly along one of 3 directions.
>
> The forces on the nonpolar groups depend on the polar groups, and
> the forces on the polar groups depend on the nonpolar groups.
> I do not know any one good way to split such forces into "hydrophobic" and
> "polar" contributions.
Average over all kinds of possible enviroments. That what
montecarlo does.
I'll comment your next paragraph here to save you of reading it
once more.
Frist, this thought experiment is less instructive that what we
can gain from simulations using the aproximations I sugest.
Second, the folding process MUST happen all the time in water
because any other scheme would change the amount of configurational space
available in such a way that it wouldn't be possible for the protein the
reach the right conformation. Now you'll say that disagree with me taking
as an exemple the membrane proteins that are sintesized in water but
their native structure must exist in nonpolar enviroment. If you want a
well folded protein in whatever solvent without the help of anything that
breakdowd constrains (such as a chaperonine) then what I said is right.
> Secondly, the folding process can be imagined as happening in many other
> orders. Each order of events leads to a different breakdown of energy
> among the different interactions. For example:
> step 1: fold up the protein in "air", not in water, but assume that
> it folds into the correct protein shape. The energy for this is negative
> and a lot of the negative energy (favorable) belongs to polar (hydrogen
> bonding) interactions. Some of the favorable interaction also belongs
> to packing (nonpolar) interactions. This can be called "nonpolar" but it
> cannot be called "hydrophobic" (yet) because there's no 'hydro' (water).
> step 2: push the folded protein into water but let the water flow through
> the greasy atoms to come close to the polar groups. This leads to more
> favorable energy. We can say that this energy also is "polar".
> step 3: "turn on" the interactions between the greasy groups and the
> water. This pushes the water away from the polar groups, and is very
> unfavorable. We can blame the nonpolar groups for this unfavorable process.
> This order of events leads to the conclusion that the polar interactions
> are favorable to folding but the nonpolar groups lead to unfavorable energies.
I hope to have clarified my points of view.
Sincerly yours,
Rafael.
*-----------------------------------------------------------------------------*
* Rafael Iosef Najmanovich Szeinfeld |SMAIL: Depto. de Bioquimica - B10 INF.*
* Dept. Biochemistry -Chemistry Inst. | Universidade de Sao Paulo *
* Dept. Math. Physics -Physics Inst. | Av. Prof. Lineu Prestes 748 *
* University of Sao Paulo | CEP 05508-900 *
* E-MAIL : szeinfel@snfma1.if.usp.br | Sao Paulo - SP - Brazil *
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