[gmx-users] Umbrella sampling with restraint on the center of mass of ligand

[Justin Lemkul]

On 1/15/20 6:32 AM, gmx user1 wrote:
> Dear GMX users
>
> I am doing umbrella sampling to obtain a PMF relative to the translocation
> of a ligand within a membrane protein.
> I want to add an harmonic potential to restrain the center of mass of the
> ligand in each window ,
> similarly to the protocols used by Subramanian et al (
> https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.8b00624 ;
> https://www.sciencedirect.com/science/article/pii/S0005273615004319?via%3Dihub
> )
>
> Yet, I am not certain of which .mdp settings I should use to accomplish my
> goal, the documentation is not clear and most infomation I find
> refers to the application of harmonic potentials when the reaction
> coordinate is a distance between two groups.

If you're not clear what the published method is or how to reproduce it, 
I suggest you contact the corresponding author and ask for sample input 
files.

> Here are my .mdp settings:
>
> pull                    = yes
> pull_print_com          = yes
> pull_print_ref_value    = yes
> pull_nstxout            = 500
> pull_nstfout            = 0
> pull_ncoords            = 1         ; only one reaction coordinate
> pull_ngroups            = 1
> pull_coord1_geometry    = direction-periodic
> pull_coord1_vec         = 0 0 1
> pull-coord1-origin      = 0 0 0
> pull_group1_name        = LIG
> pull_coord1_groups      = 0 1
> pull_coord1_type        = umbrella  ; harmonic potential
> pull_coord1_start       = yes       ; define initial COM distance > 0
> pull_coord1_rate        = 0.0       ; restrain in place
> pull_coord1_k           = 500      ; kJ mol^-1 nm^-2
>
> Essentially, I created a vector between the center-of-mass of the ligand
> and an absolute reference (0,0,0) and I had to use pull_coord1_geometry =
> direction-periodic ( instead of direction) ,because the simulation crashed.
> This also forces me to perform an NVE simulation.
>
> Is this the right way of applying a an harmonic restraint on the
> center-of-mass of a ligand for umbrella sampling? Are these settings
> correct?

If you're looking at ligand translocation across a membrane, you should 
not be using (0,0,0) as a reference. The conventional reaction 
coordinate is the normal to the bilayer, so the reaction coordinate 
connects the COM of the bilayer with the COM of the ligand along the z-axis.

-Justin

-- 
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Justin A. Lemkul, Ph.D.
Assistant Professor
Office: 301 Fralin Hall
Lab: 303 Engel Hall

Virginia Tech Department of Biochemistry
340 West Campus Dr.
Blacksburg, VA 24061

jalemkul at vt.edu | (540) 231-3129
http://www.thelemkullab.com

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