[gmx-users] FEP in sugar

[hugo verli]

Hi to all,

in previous mails I put some doubts in the list about the conversion of a chair
conformation in a boat conformation using free energy perturbation. I apologize
for the insistence in this subsject but I realy need your assistence.

The chair->boat transformation occurs only in vacuum. The same transformation
with the same parameters did not occurs in water. I try to use exclusions of
non
bonded interactions in .mdp file, but these exclusions abolish the
transformation in vacuum
and did not modify the water transformation (still not occur).

The boat->chair transformation still occurs in vacuum only with exclutions for
non-bonded interactions inside the molecule. The same transformation did not
occur in water. It appears to me
to be dued to strong intramolecular hydrogen bonds between a hydroxyl and a
sulphate group not broken in the FEP calculations. Does it make sense?

So I have two problems:
1) In vacuum, the chair->boat transformation occurs without exclusions, while
the boat->chair transformation only occurs with exclusions.
2) The transformation in vacuum is only a test. I need to perform it in water.
But in water the two transformations did not occur.

I should remember that both transformations occur both with minimization and
short molecular dynamics (<25ps) (both in water) so the the improper dihedrals
added in topology are well describing the two conformations.

Could these problems be dued to dificulties of the gmx forcefield in simulate
sugars? The topology for the sugar was generated with prodrg.
Or these problems can arise from the strong intramolecular interactions?
Is there any way to overcome these problems? I can make the two transformations
only changing the topology lines and runing a new dynamics. But doing so I will
neglet the energy information about the transformation.

Many thanks in advance and apologize for the insistence.


Hugo Verli.