Hello again,
while waiting for the response to my questions I did small progress which
suggests that the reported differences (really huge in case of phenol) are
probably
really just due to different charge parametrization (Amber versus Charm).
A)
I repeated calculation of dG_bulk_elec of phenol using input files from
tut. A9
and have obtained value -38.49138 kcal/mol which is almost identical with
the
previously reported value ( -38.64 see below) which is really different
from
the value reported in below mentioned article ( -6.03 kcal/mol).
B)
I did the same calculation (i.e. free energy contribution connected with
turning on
ligand charges in bulk water) for the benzene and obtained value -0.27
kcal/mol,
which is also in this case different from the value -1.86 kcal/mol
reported in the
article however the difference is now much smaller than in case of phenol.
This suggests that problem is really in different charge parametrization
and in case of
phenol mainly charge parametrization of the OH group where are probably
significant differences.
Here probably the parametrization from the article is more realistic than
in tutorial as the reported experimental value
for the whole solvation free energy is in case of phenol -6.62 kcal/mol
which is much closer to calculated
value from the article (-4.68 kcal/mol), than calculated value using
tutorial A9 input files (-37.2 kcal/mol).
In case of benzene the situation is much better.
As I reported before the agreement in vdw part (tutorial versus article)
is almost perfect (calculated/compared just in case
of phenol)
Best wishes,
Marek
Dne Mon, 23 Apr 2012 18:55:26 +0200 Marek Maly <marek.maly.ujep.cz>
napsal/-a:
> Hello all,
>
> after successful passing through the Thomas's TI tutorial (TUTORIAL A9:
> Thermodynamic Integration using soft core potentials) I
> started to work on reproducing some numbers from the article:
>
> -------------------------------------------------------------------------------------
> Y. Deng and B. Roux: Calculation of Standard Binding Free Energies:
> Aromatic
> Molecules in the T4 Lysozyme L99A Mutant,J. Chem. Theory Comput. 2006, 2,
> 1255-1273
> --------------------------------------------------------------------------------------
>
> which is also one of the reference from Amber manual and also it was
> partially inspiration regarding above mentioned
> tutorial.
>
> The reason why I moved here is that I am interesting about the
> calculation
> of the absolute free binding energies using TI
> (not only relative ones).
>
> As one of the easiest part of reported calculations is calculation of
> energy change connected with turning on/off electrostatic
> and vdw interactions between ligand and solvent in bulk solvent I started
> to reproduce this energy (dG_bulk_int) in case of phenol.
>
> In above mentioned article they have obtained the total free energy
> change
> connected with turning on el. and vdw interaction
> of phenol with water in bulk water equal to dG_bulk_int = -4.68 kcal/mol
> where vdw contribution is dG_bulk_vdw=1.34 kcal/mol and electrostatic
> contribution
> is dG_bulk_elec=-6.03 kcal/mol.
>
> I have obtained dG_bulk_int = -37.2 kcal/mol where vdw contribution is
> dG_bulk_vdw = 1.44 kcal/mol and electrostattic contribution
> is dG_bulk_elec = -38.64.
>
> As we can see, the agreement of vdw contribution is quite satisfactory
> (considering all eventual differences in "parameters" used e.g. ff,
> lambda
> points, vdw TI "mixing" method,
> numerical integration method ... ) but in case of energy connected
> with
> turning on the electrostatic interactions between phenol and water there
> is huge discrepancy
> (-6.03 versus -38.64 kcal/mol).
>
> I would be very grateful for any relevant comments/suggestions which
> might help me to learn the reason of such huge difference which
> probably could not stem from the eventual small differences in phenol
> partial charges in both cases or differences in MD methodology
> (spherical water shell versus water box). The water model is also the
> same in both cases (TIP3P).
>
>
> I used the input files which are practically identical with those from
> the tutorial A9. I just recreated new
> prmtop/incprd files (phen_w.prmtop/phen_w.incprd and w.prmtop/w.incprd
> )
> using that Thomas's ones (phn.prm/phn.rst) as I needed also the empty
> water box.
> I used the same library (phen.lib) in creating input files from the
> relevant pdbs. The used script for the preparation of all mdin/group
> files and to run calculation is also just a slightly modified Thomas's
> "prepare_example.sh" here I just introduced the reverse processes
> (turning off the vdw and el. interactions) so the results (dGs) have
> just
> opposite sign comparing to those reported above.
>
> All the input files and the general scripts are attached.
>
> Thanks a lot in advance to help me understand !
>
> Best wishes,
>
> Marek
>
>
>
>
>
>
>
>
>
>
>
>
>
>
> --
> Tato zpráva byla vytvořena převratným poštovním klientem Opery:
> http://www.opera.com/mail/
>
--
Tato zpráva byla vytvořena převratným poštovním klientem Opery:
http://www.opera.com/mail/
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Received on Tue May 01 2012 - 20:30:03 PDT
