[gmx-users] Rugged dG/dlambda when turning off charges
Robert Johnson
bobjohnson1981 at gmail.com
Thu Jan 31 19:07:15 CET 2008
Thanks Maik for your advice. I think what I'm going to do is to look
at the relative binding free energy differences between the bases.
Thus, I will morph the bases into one another, leaving the sugar and
phosphate intact. Do you think this is a better strategy?
Thanks,
Bob
On 1/28/08, Maik Goette <mgoette at mpi-bpc.mpg.de> wrote:
> OK, forget my first reply and the mentioned topology splitting ;)
> It MAY be a problem, that you switch off two charged molecules, but I
> really dont know, if this is the problem.
> Try some totally artificial process, where you build a neutral base and
> use no counterion and morph the neutral base away.
> From my experience with DNA I can tell you, that these huge
> fluctuations are quite intrinsic due to the size of the perturbation.
> Actually, I don't have an idea, how to get rid of them.
> Trying to sample much longer could help to converge the system.
> Furthermore, using more lambda-steps could help you in getting a better
> total error and stuff.
> Again, from my experience I can tell you, that calculating free energies
> from letting nucleotides appear/disappear is really no fun.
> If you come up with a solution yourself, I would be highly interested in it.
>
> Regards
>
> Maik Goette, Dipl. Biol.
> Max Planck Institute for Biophysical Chemistry
> Theoretical & computational biophysics department
> Am Fassberg 11
> 37077 Goettingen
> Germany
> Tel. : ++49 551 201 2310
> Fax : ++49 551 201 2302
> Email : mgoette[at]mpi-bpc.mpg.de
> mgoette2[at]gwdg.de
> WWW : http://www.mpibpc.gwdg.de/groups/grubmueller/
>
>
> Robert Johnson 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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