Hi Kepa,
what you see is not necessary a problem. Bear in mind that TI
transformation results are not physically meaningful without embedding
them into a thermodynamic cycle, especially individual simulation steps
with non-existent end states.
Furthermore, in this case, note that you are changing forcefield
intramolecular energies, the absolute values of which are completely
non-physical. The 1-4-EEL interaction are particularly important here and
easily amount to 100 kcal/mol or so. Look at the DVDL breakdown to find
out which terms contribute most to your dvdl.
For the system you study, would you expect MD free energy calculation to
produce a good result? The different glucose isomers should differ in ring
strain and 1-4 interactions, terms that might need to be determined
quantum mechanically.
Kind Regards,
Thomas
On Fri, January 25, 2013 8:42 am, Kepa K. Burusco wrote:
> [25-I-2013]
>
> Hi everybody,
>
> I'm a newcomer to Thermodynamic Integration calculations and I have been
> doing some tests running a TI to transform the alpha anomer of glucose
> into the beta anomer to determine the Difference in Free Energy. I am
> using Amber11 with AmberTools12 and Glycam06h force field. I am
> following the tutorial A9 (http://ambermd.org/tutorials/):
>
> 1) First of all I created the input files for the alpha and beta anomers
> and solvated them with TIP3P (glaWAT glbWAT) taking care of all the
> requierments needed to avoid problems with common/special atoms.
> 2) Then I divided TI process into 3 Legs: switching off all the charges in
> the glucose, mutating atoms (employing soft-core potentials), and then
> again switching on the charges (files *.in).
> 3) I extracted the lines "DV/DL average" and "DV/DL fluctuations" from
> output files to create the 3 columns (Lambda, Average, Fluctuation) text
> file as recommended by the tutorial ("stepX.TIresults.txt").
> 4) Finally, I processed the lines with the perl script in tutorial
> ("TotalTI.stepA.txt").
>
> After checking the results I have discovered something strange, and I
> would like to ask you if I have been anything wrong.
>
> In the first leg, I switch off the charges of the glucose molecule. Since
> it is a polar one, interaction with water should be favorable and
> therefore going from the molecule with charges (polar) to the molecule
> without charges (apolar) should give a positive difference in energy.
> Instead, the difference in free energy is about -91.8 kcal/mol (???).
> We find exactly the same strange result in the third leg when I apply the
> charges. Going from the apolar molecule in water to the polar molecule
> should be favoured, however, I again find the wrong sign in the energy
> (about +92.5).
>
> I send you attached a tar file with the text documents (submitting scrips,
> input files, structures, results...)
> Does anyone have any clue about what I am doing wrong?
>
>
> Than you very much.
>
> Kepa K.
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>
Dr. Thomas Steinbrecher
formerly at the
BioMaps Institute
Rutgers University
610 Taylor Rd.
Piscataway, NJ 08854
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Received on Fri Jan 25 2013 - 09:00:03 PST
