[gmx-users] Distance for window spacing in US?

Andrei Neamtu neamtuandrei at gmail.com
Fri Feb 22 12:40:02 CET 2013

As i understand, if pulling geometry is set to  'pull_geometry = distance'
and 'pull_dim = Y Y Y" then the DISTANCE between the COM of the enzyme and
the ligand is restrained with the umbrella potential. If using long enough
simulation times for each restraint umbrella window, as long as the ligand
leaves the binding site it can freely diffuse in the space around the
enzyme as only the distance between COMs is restrained, is this correct?
And if using let's say 'pull_dim = Y N N' it can freely diffuse away in the
YZ plane while keeping to a certain extent the X distance constant in each
window. Is there a way to stop this diffusion to let the ligand move only
on X direction?
Maybe I put a trivial question (sorry for this :) ) but I cannot see why
restraining only in one direction let's say X if the ligand will diffuse in
the YZ plane? I'm facing the same problem with a host - guest complex. I
tried both the 'pull_dim = Y Y Y' (and the guest started to diffuse around
the host after a certain distance, 4 ns on each window) and 'pull_dim = N N
Y' ( and the guest diffused in the XY plane).
But, in principle .. the free energy being a state function it does not
matter which way the process of dissociation takes place as long as you
pull away to sufficient distance the ligand  from the host (or enzime),
considering of course the distance between the COMs as the reaction
coordinate. This of course if one is interested only in the free energy

Best regards,


On Fri, Feb 22, 2013 at 10:33 AM, Erik Marklund <erikm at xray.bmc.uu.se>wrote:

> On Feb 22, 2013, at 1:13 AM, Justin Lemkul wrote:
>> On 2/21/13 6:24 PM, Yun Shi wrote:
>>> So in umbrella sampling, does it really matter if the vector
>>> connecting the COMs of protein and ligand is NOT parallel with the
>>> vector of the pulling force (although the pull rate is 0)?
>>> I guess as long as the force in each sampling window is along the same
>>> direction, we can in theory get potential of mean force along any
>>> direction.
>> I honestly don't know how that would affect things.  Perhaps someone else
>> who has dealt with such cases can comment, but typically it is easiest to
>> define the reaction coordinate to be coincident with the direction(s) along
>> which you wish to apply the umbrella restraint.
>> -Justin
> The important thing is that your PMF is calculated along a sensible
> reaction coordinate. In the worst case there may be free energy barriers
> perpendicular to your coordinate which the system would have to cross.
> Those will be important for the kinetics and thermodynamics that you aim to
> study, but will not appear in your PMF.
> Erik
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