From: Sébastien Légaré (Sebastien.Legare_at_rsvs.ulaval.ca)
Date: Thu Dec 10 2009 - 14:19:01 CST
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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