[gmx-users] Free energy of discharging and then recharging not zero

[Maik Goette]

Hi Robert

I wouldn't expect that either. Morphing G to A should yield quite 
reasonable results, cause you just have few dummies in your system.
The process, you describe is the way, one would think of, yes.
Just to get you right. Are you swithing off charges of a whole base or 
nucleotide? In the case of a nucleotide, you morph away one netto 
charge. That could be problematic with PME (?). Maybe trying reaction 
field could help here.

Now, if you turn off the charges of the base and then turn it on again, 
both contributions should actually lead to the same values, as David said.
As long, as no dummies are involved, everything should run smooth. I 
suggest, you simply do position restrained simulations at the discrete 
lambda steps, when turning on/off your charges. Maybe, they converge 
faster then. This would indicate a sampling problem, indeed.

For a purine to pyrimidine morph (or vice versa), I'm still convinced, 
that you would have to sample for ages to get a converged system, though.

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:
> Hi Maik,
> That's exactly what I'm attempting to do...morph G to A etc. All I'm
> doing here is turning off the charges of G and then turning them on
> again. Wouldn't you do this anyway in the morph step? Wouldn't the
> process go something like: Turn off charges -> Morph LJ parameters ->
> Turn on charges.
> 
> It seems like I've got to be doing something wrong. I can't believe
> that simply turning off/on the charges would drastically perturb the
> entire system and prevent convergence.
> Bob
> 
> 
> On Thu, May 8, 2008 at 6:12 AM, Maik Goette <mgoette at mpi-bpc.mpg.de> wrote:
>> Hi Robert
>>
>>  Sounds familiar to me. I also tried to compute free energy differences by
>> letting whole bases appear/disappear. I ran into the same problems and
>> haven't found a solution yet. Probably the perturbation is too large to gain
>> converged results. My solution was stopping those simulations.
>>  This doesn't sound promising, I know, but actually, I fear, there is no
>> proper solution. Maybe you should morph G to A or T to C or something like
>> that, where just a few atoms have to be perturbed.
>>
>>  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:
>>
>>>
>>>
>>> Hello everyone,
>>> I'm trying to calculate the free energy of binding of DNA bases on a
>>> carbon nanotube. I'm running some tests to make sure that I'm doing
>>> everything correctly. One thing I tried was turning off all the atom
>>> charges of the DNA base and then turning them back on again.
>>> Theoretically, the free energy changes of these two processes should
>>> be equal and opposite and thus sum to zero. However, this is not what
>>> I'm finding.
>>>
>>> For guanine, I get a free energy change of 648 kJ/mol and -618 kJ/mol
>>> for turning off and turning on the charges, respectively. Obviously,
>>> they are not equal by 30 kJ/mol, which seems pretty big. I have done
>>> some error estimation using the g_analyze -ee program. One thing I
>>> find strange is that the error estimates in dV/dl for TURNING ON the
>>> charges is large (over 2) and do not even converge for a 7.5 ns
>>> simulation. In contrast, the error in dV/dl for TURNING OFF the
>>> charges converges extremely quickly (using small block sizes of 50 or
>>> less) and is smaller at 0.3. So it seems like I have some sampling
>>> problems with the TURNING ON portion. Is there some reason why you
>>> must sample a longer trajectory when turning on the charges?
>>>
>>> I'm following the procedures of
>>> http://www.dillgroup.ucsf.edu/group/wiki/index.php/Free_Energy:_Tutorial
>>>
>>> Does anyone know the reason for the discrepancy between these two
>>> (seemingly identical) processes?
>>>
>>> Thanks,
>>> Bob
>>>
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