[gmx-users] Rugged dG/dlambda when turning off charges

[David Mobley]

Bob,

Right, exactly. What I recommend is to turn off the charges with
sc_alpha set to zero, and only use sc_alpha nonzero when changing VdW
interactions.

See for example Guideline 4 here:
http://www.alchemistry.org/wiki/index.php/Best_Practices

(FWIW, this is our attempt to compile some general "best practices"
for free energy calculations, but it's still in progress. It's
publicly editable).

David


On Jan 25, 2008 3:26 PM, Robert Johnson <bobjohnson1981 at gmail.com> wrote:
> Thanks David,
> Since I'm turning off the VdW parameters as a second step, there
> really isn't any reason to use the soft core potentials when turning
> off the charges right? Thus, sc_alpha should be set to zero when
> turning off charges?
> Thanks,
> Bob
>
> On Jan 25, 2008 5:38 PM, David Mobley <dmobley at gmail.com> wrote:
> > It will only be smooth if you don't use soft core (i.e. sc-alpha =0 ).
> >
> > Best,
> > David Mobley
> > http://www.dillgroup.ucsf.edu/~dmobley
> >
> >
> > On Jan 25, 2008 12:40 PM, Robert Johnson <bobjohnson1981 at gmail.com> wrote:
> > > Hello everyone,
> > > As I mentioned in a previous post, I'm trying to compute the free
> > > energy of binding of a DNA base on a carbon nanotube. My system
> > > consists of a single DNA nucleotide (base, sugar, phosphate group) on
> > > a rigid carbon nanotube in aqueous solution. A single Na+ counterion
> > > is also included for charge neutralization. I'm proceeding with this
> > > by computing the free energy associated with the following
> > > transformations:
> > >
> > > Water + Nanotube + DNA + Na+ -> Water + Nanotube + Nothing
> > > Water + DNA + Na+ -> Water + Nothing
> > >
> > > For each of these transformations I FIRST turn off the charges on the
> > > base and counterion over a set of 5 lambda values (0.0, 0.25, 0.5,
> > > 0.75, 1.0). From literature and other posts on the GMX mailing list,
> > > it seems like this small set of values should be adequate because
> > > dG/dlambda tends to be pretty smooth for discharging the molecule.
> > >
> > > Unfortunately, that doesn't seem to be the case in my system. Here is
> > > a table of the dG/dlambda values I get from running 5 ns trajectories
> > > of my system:
> > >
> > > lambda     <dG/dlambda>
> > > 0.0           6211.105
> > > 0.25         1055.254
> > > 0.5           1230.675
> > > 0.75         1128.359
> > > 1.0           756.2904
> > >
> > > If you plot this you will see a large drop from lambda=0 to 0.25. Then
> > > dG/dlambda increase slightly from lambda=0.25 to 0.5 and then smoothly
> > > decreases after that. This seems like a pretty strange result. Also,
> > > it seems that something weird is going on around lambda=0. If I
> > > compute dG/dlambda for lambda=0.05, I get something around 1200-1300,
> > > which is again a very sharp decrease from the value of 6211.105 I get
> > > at lambda=0. Thus, it doesn't seem like simply adding more lambda
> > > values is going to help me.
> > >
> > > Here are the values I'm using for the free energy calculation:
> > > free_energy         =  yes
> > > init_lambda         =  0.05
> > > delta_lambda        =  0
> > > sc_alpha            =  0.5
> > > sc_power            =  1
> > > sc_sigma            =  0.3
> > >
> > > Also, here is an excerpt from my topology file:
> > > [ atoms ]
> > > 1       P       1       DG      P       1       1.1659  30.9700
> > >  P       0.0000  30.9700
> > > 2       O       1       DG      O1P     1       -0.7761 16.0000
> > >  O       0.0000  16.0000
> > > 3       O       1       DG      O2P     1       -0.7761 16.0000
> > >  O       0.0000  16.0000
> > >
> > > I'm not perturbing any of the bonding interactions or VdW parameters -
> > > I'm just turning off all charges on the molecule.
> > >
> > > Does anyone have any ideas or suggestions about how this can be improved?
> > >
> > > Thanks,
> > > Bob Johnson
> > > _______________________________________________
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