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

[Robert Johnson]

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