[gmx-users] RE: Gibbs Energy Calculation and charges

[Dallas Warren]

Michael, thanks for taking the time to comment and have a look.

The real issue I am having is a bit deeper into the topic than that, my last reply was just an observation on something else.  Will summarise what I have been doing etc.

I have a molecule that are calculating the Gibbs energy of hydration and solvation (octanol).  In a second topology the only difference is that the atomic charges have been doubled.  Considering that charges are scaled linearly with lambda, the normal charge values of dH/dl from lambda 0 to 1 obtained should reproduce that of the double charged molecule from lambda 0.5 to 1.0.  Is that a correct interpretation?  Since the only difference should be that charge of the atoms and over that range the charge will be identical.

I was using couple-intramol = no and the following are the results from those simulations.

For the OE atom within the molecule, I have plotted the following graphs of dH/dl versus charge of that atom for both of the topologies.
	octanol - http://ozreef.org/stuff/octanol.gif
	water - http://ozreef.org/stuff/water.gif
	mdp file - http://ozreef.org/stuff/gromacs/mdout.mdp

The mismatch between the two topologies is the real issue that I am having.  I was hoping to get the two to overlap.

My conclusion based on this is that there is actually something else being changed with the topology by GROMACS when the simulations are being run.  The comments in the manual allude to that, but not entirely sure what is going on.

> From the manual:
>________________________
>couple-intramol:
>
>no
>         All intra-molecular non-bonded interactions for moleculetype
>couple-moltype are replaced by exclusions and explicit pair
>interactions. In this manner the decoupled state of the molecule
>corresponds to the proper vacuum state without periodicity effects.
>yes
>         The intra-molecular Van der Waals and Coulomb interactions are
>also turned on/off. This can be useful for partitioning free-energies
>of relatively large molecules, where the intra-molecular non-bonded
>interactions might lead to kinetically trapped vacuum conformations.
>The 1-4 pair interactions are not turned off.

Chris Neale commented:
>Ah, I see. I guess that you are using couple-intramol = no (the default in v4.6.3 at least). That means
>that the intramolecular charge-charge interactions are always at full-strength (and therefore different).
>I would expect that normal at lambda=0 should be the same as double at lambda=0.5 only for
>couple-intramol = yes
>If you were using couple-intramol = yes already, then I am as confused as you are.

>From Chris' comment, I then went back and repeated the calculation using couple-intramol = yes with the results of this in the below image (plus the previous when set to no for comparison)

http://ozreef.org/stuff/gromacs/couple-intramol.png

My rather garbled comment that you saw was my attempt to make sense of the fact that this setting made things worse (and try to add something to get this issue to have another pass on the list, hoping someone like yourself will comment), and the value of dH/dl for c-i=yes at lambda=1 matches with c-i=no at lambad=0.  This you can see with the previously linked to graphs.

Hopefully that helps understand what I have been doing and the issues.

Catch ya,

Dr. Dallas Warren
Drug Delivery, Disposition and Dynamics
Monash Institute of Pharmaceutical Sciences, Monash University
381 Royal Parade, Parkville VIC 3052
dallas.warren at monash.edu
+61 3 9903 9304
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When the only tool you own is a hammer, every problem begins to resemble a nail.