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

[Joerg Sauter]

On 08/05/2013 01:54 PM, Justin Lemkul wrote:
>
>
> On 8/5/13 7:44 AM, Joerg Sauter wrote:
>> 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.
>>
>
> Have you tried running with rlist=rcoulomb=rvdw = 0 rather than 99?  
> If nothing else, I would try again with version 4.6.3.  There have 
> been tons of fixes to the free energy code since 4.6.1, though I don't 
> know offhand which, if any, would be affecting your results.  
> Regardless, the current version should always be the "best" version ;)
>
> -Justin
>
Hi Justin,

I just tried it with version 4.6.3. and rlist=rcoulomb=rvdw = 0. 
Unfortunately, I get the same results.

Best,
Joerg