[gmx-users] Docked ligand, umbrella sampling and "aiming"

[Jernej Zidar]

Hi there,
  I have a receptor with a docked ligand. I would like to perform an
umbrella sampling simulation to get some insights into the
thermodynamics of the binding.

  Following the Umbrella Sampling tutorial I performed the 500 ps
pulling simulation. A visual examination of the trajectory revealed
there's an expected change in the position of the ligand that is
coincidental with a worryingly big increase in the force exerted on
the ligand. Link to a figure:
https://www.dropbox.com/s/fj3daaagimuynni/rec-lig-pos-for.pdf?dl=0

  Is this an expected behaviour or should I try to somehow adjust the
direction of the pulling? If so, could you advise on a strategy to do
so?

Thanks in advance,
JZidar