[gmx-users] Rugged dG/dlambda when turning off charges
Maik Goette
mgoette at mpi-bpc.mpg.de
Fri Feb 1 08:39:19 CET 2008
As long as you morph pyrimidine into pyrimidine and purine into purine,
everything is fine, I'd say.
Morphing a pyrimidine into a purine is really problematic, cause you
have to morph the whole nucleoside. Until now I didn't find a
possibility to do that without perturbing all atoms of the base, which
leads to a very heavy perturbation and therefore a very "spiked" dG/dl.
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 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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