[AMBER] Huge discrepancy in el part of "solvation energy" using Thermodynamic Integration

From: Marek Maly <marek.maly.ujep.cz>
Date: Mon, 23 Apr 2012 18:55:26 +0200

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:
Molecules in the T4 Lysozyme L99A Mutant,J. Chem. Theory Comput. 2006, 2,

which is also one of the reference from Amber manual and also it was
partially inspiration regarding above mentioned

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
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,


Tato zpráva byla vytvořena převratným poštovním klientem Opery:  
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Received on Mon Apr 23 2012 - 10:30:03 PDT
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