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

Robert Johnson bobjohnson1981 at gmail.com
Wed May 7 22:48:53 CEST 2008


Hi David,
Yes...sorry...I'm doing a 7.5 ns for each lambda value (lambda = 0,
0.25, 0.5, 0.75, 1.0). Every single simulation takes place from the
exact some starting configuration. No restraints are being used. The
calculation I'm planning on doing (once everything is worked out) is a
relative binding free energy calculation where I morph G to A. But for
now I'm just taking G and turning the charges off and then turning
them back on. I do not perturb the LJ parameters at all so I'm not
using soft-core potentials or any of that stuff.

The trajectories are all qualitatively the same - irrespective of
lambda value. The base adsorbs very strongly to the nanotube. For each
trajectory, the base simply diffuses around on the surface of the
nanotube. To the base, the nanotube appears almost as a uniform
cylinder - the base feels very little corrugation. Plus, there is no
electrostatic interaction between the base and the nanotube. It is
completely a van der Waals effect. Thus, the base doesn't have the
chance to desorb because I'm not perturbing the LJ parameters.

It seems that in all the trials I have done, I always obtain a larger
error that doesn't converge whenever I turn ON charges. I don't really
see anything drastically different occuring in any of the
trajectories, so it's hard to believe that it could be a sampling
problem.
Bob


On Wed, May 7, 2008 at 4:12 PM, David Mobley <dmobley at gmail.com> wrote:
> Bob,
>
>
>  > 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?
>
>  Er, can you provide a few more details here? i.e., when you say "a 7.5
>  ns simulation", do you mean 7.5 ns at each lambda value? (I appreciate
>  that you're doing the error analysis separately at each lambda,
>  though).
>
>  Are you restraining the base to be near the nanotube in a particular
>  orientation? For example, I could imagine that if the base had drifted
>  away from the nanotube after turning off the charges, then it might be
>  hard to converge the calculation for turning on the charges (and the
>  calculation for turning off the charges would probably not be
>  converged either, though it might appear converged).
>
>  The only reason I can see why you might have different convergence
>  properties for turning on the charges than turning off the charges is
>  if the starting state in the two sets of simulations is different (or,
>  if you are starting the simulation at each lambda value from the end
>  point from the preceding lambda value). Are you doing one of those
>  things?
>
>  David
>
>
>  >  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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