[gmx-users] Unphysical conformations in decoupled free energy simulation

[Joerg Sauter]

Dear all,

I am trying to compute the free energy of hydration for cellobiose (a 
beta (1-4) glucose dimer) using BAR in Gromacs 4.6.1. However, I 
encounter a problem.

I find that the vacuum conformations of the molecule in a regular vacuum 
simulation differ from the conformations in the decoupled simulation in 
the free energy case i.e., with the additional mdp entries:

free-energy              = yes
init-lambda                 = 0
couple-lambda0           = none
couple-moltype           = solute
couple-intramol          = no

Here is a histogram of the dihedral angles of the glycosidic linkage in
the vacuum case
https://dl.dropboxusercontent.com/u/70358077/reg.pdf (it stays in the 
global free energy minimum)
and this is the decoupled free energy case (same starting conformation 
in the global free energy minimum)
https://dl.dropboxusercontent.com/u/70358077/fe.pdf

I understand that Gromacs replaces the intramolecular interactions with 
explicit pair
interactions. Therefore, I had to increase table-extension but that did 
not change much. I was thinking that maybe this could be a problem 
specific to this topology (a GLYCAM06h conversion from Amber), however, 
I do not see how this can occur.
I hope someone has an idea what is going wrong.

mdp file:    https://dl.dropboxusercontent.com/u/70358077/md.mdp (same 
behaviour for longer runs)
top file:    https://dl.dropboxusercontent.com/u/70358077/cellob.top
gro file:    https://dl.dropboxusercontent.com/u/70358077/cellob.gro

This is sort of a minimal example. The same problem occurs
in a regular simulation when decoupling from water using multiple lambdas.

Thank you,
Joerg