[gmx-users] Umbrella Sampling and flat-bottom position restraints

Oliver Stueker ostueker at gmail.com
Sun Nov 16 19:04:20 CET 2014

Dear fellow Gromacs Users,

I'm trying to calculate the binding free energy between a protein and a
small molecule using Umbrella Sampling.

I made my first attempt last year using Gromacs 4.5 and ran into the same
convergence problems that have been pointed out on the mailing list several
To overcome these problems I now want to give it another try utilizing the
flat-bottomed position restraints that have been introduced in Gromacs 5.0.

My plan is to perform the Umbrella sampling along the Z-axis and to
restrict the protein as well as the ligand with flat-bottomed position
restraints along X and Y into a cylindrical space (as suggested e.g. by
Chris Neale in [1]).

But I'm not quite sure what radius the cylinder should have ( or how wide
the flat bottom should be).
The protein is roughly spherical with a diameter of ~4nm. I was initially
thinking to use an r_{fb} of 2nm for the protein and  for the ligand 1/2 of
it's longest dimension to allow both of them to re-orient freely. But the
more I think about, I'm afraid that it's too large.

Has anyone have experience with that? Maybe even a published paper?
So far I've unsuccessfully tried several times to find a published method.

Also to I need to consider the flat-bottomed potential when doing the
g_wham analysis?



More information about the gromacs.org_gmx-users mailing list