From: Mert Gür (gurmert_at_gmail.com)
Date: Tue Dec 15 2009 - 02:48:31 CST
Dear Pu,
Since I am using water (in all simulations) as its particular solvent
environment, shouldn't I be on the same FEL for each different simulation
conditions?
Dear Sébastien,
Thanks for this detailed e-mail. It was quite useful and informative. As you
imply absolute free energy calculations seem not to be straightforward
therefore I think I will stick only with the provided methods to evaluate
free energy difference for now.
I believe due to our point of view ,our understanding of work potential is
different. I still believe that water can be treated as an T,P reservoir
since waters temperature and pressure is constant.
Best,
Mert
2009/12/10 Sébastien Légaré <Sebastien.Legare_at_rsvs.ulaval.ca>
> Hi Mert,
>
> > I am comming from an mechanical enginnering background and it keeps
> > bothering me how much work potential a protein has at a sepecific
> > temperature, and pressure.
>
> It is really interesting to compare the points of view of mechanical
> engineers
> and computational chemists on work potential. There are some points on
> which
> I do not agree with you.
>
> If by "how much work potential a protein has" you mean the energy required
> to
> take every atom of the protein from infinity and bring them at a given
> protein conformation, a molecular mechanics force field can not provide the
> correct energy since it can not compute the energy required to form
> covalent
> bonds.
>
> > I have given the issue a second tought. I think it is not wrong to treat
> > the solvent as an T,P reservoir for the protein.
>
> Considering the importance of hydrophobic effects on protein folding, I
> think that water can not be seen as a simple T,P reservoir. Any change in
> the
> protein can require a reorganisation of water around it. The water
> reorganisation free energy must be included if one wants to know the
> work between two protein states. The solvent reorganisation free energy
> could be approximated by implicit solvent calculations.
>
> > The expression I have provided evaluates the free energy relative to an
> > ideal gas reference state E_i=0
> > F=-kT ln[ <exp(b E_i)> ]
>
> If the ideal gas state you refer to is the folded protein in vacuum, its
> energy for any configuration i will not be 0. If the ideal gas state is a
> "gas protein", where the atoms of the protein are unbound from each other
> and
> form a gas, then E_i=0. But the folded protein and this gas protein have
> VERY
> different conformations and the provided expression does not hold anymore
> (if
> I am not mistaken that this is the standard FEP equation).
>
> > ...
> > entropy to converge. This procedure I am intending was supposed to be
> > straightforward
>
> Absolute free energy calculation from MD is not straightforward. Free
> energy
> differences are more easily calculated but many technical problems can
> complicate it.
>
> Regards
>
> Sébastien Légaré
>
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