[gmx-users] pmf settings

[Justin Lemkul]

On 11/17/16 5:33 AM, Qasim Pars wrote:
> Dear users,
>
> I am trying to calculate the binding free energy between protein and ligand
> using the PMF. I will add the below pull code lines to my production run
> mdp file.
>
> pull            = umbrella
> pull_geometry   = distance
> pull_dim        = Y Y Y
> pull_start      = yes
> pull_ngroups    = 2
> pull_group0     = protein
> pull_group1     = ligand
> pull_init1      = 0
> pull_rate1      = 0.0
> pull_k1         = 5000
> pull_nstxout    = 1000
> pull_nstfout    = 1000
>
> My questions are:
>
> -According to the above lines the binding free energy is calculated for the
> center of mass of each group, right?
>

The binding free energy is calculated as a function of the reaction coordinate 
defined by the respective centers of mass.  You don't calculate a free energy of 
a center of mass.

> -Is it necessary to add the above lines in the nvt.mdp and npt.mdp file as
> well?

Yes, equilibrate under the conditions you want to simulate.  If you don't, the 
separation between the protein and ligand will vary, and your use of "pull_start 
= yes" and "pull_init1 = 0" may not mean what you want it to by the time you get 
to production because things will have moved around.

>
> -how can I set/change the number of windows used in the Umbrella Sampling
> calculations?
>

These are all just independent simulations.  See my tutorial for an example:

http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html

> -To get the accurate binding energy should I use some specific atoms of
> each group (for instance: ligand N1 and protein C15) or the center of mass
> of each group?
>

No.  You may bias the result even more and potentially inhibit sampling.

-Justin

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================