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

[Maik Goette]

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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