[gmx-users] PMF profile from Umbrella - Plateau

Justin A. Lemkul jalemkul at vt.edu
Wed May 16 17:20:01 CEST 2012

On 5/16/12 11:16 AM, Steven Neumann wrote:
> On Wed, May 16, 2012 at 3:38 PM, Justin A. Lemkul <jalemkul at vt.edu
> <mailto:jalemkul at vt.edu>> wrote:
>     On 5/16/12 10:25 AM, Steven Neumann wrote:
>         Dear Justin,
>         I pulled my ligad away of 6nm from the protein and obtained beautiful
>         and smooth
>         curve of PMF using 28 windows. Starting from zero kcal/mol corresponding
>         to app
>         0.3 nm then minima and curve increase till my plateau which starts from
>         app 1 nm
>         - then I have nearly straight line till 6.3 nm.
>         My question: Can I decrease pulling distance to save time for the future
>         simualtions with this system in terms of number of water molecules?
>         Shall I just
>         pull it away of 2-3 nm and I will obtain the same deltaG?
>     Ideally, one would separate the molecules such that they are no longer
>     interacting.  Obviously with methods like PME this is impossible, so what
>     you're after is sufficient separation such that there is negligible
>     interaction between the protein and ligand.  The required distance depends
>     on the nature and size of the ligand, the types of interactions it
>     experiences, and the cutoffs used. Keep in mind that even if a molecule is
>     beyond the longest nonbonded cutoff, there are still effects like water
>     ordering that can persist up to about 1.0 nm, so I would certainly make sure
>     that all the atoms of the ligand and protein are separated by a minimum of
>     twice the longest cutoff or so to account for this effect.  Note that this
>     would imply the use of g_mindist, not g_dist, as the distance I'm talking
>     about is not the same as the COM distance.
>     That's just my own rule of thumb for an initial check; you'll have to
>     analyze your own system to decide what's happening and what you should do.
>     -Justin
> Thanks Justin! I totally agree. But now having my ligand pulled 6 nm away and
> obtained deltaG= -4.5 kcal/mol. In theory when I use all windows till 3.5 nm
> (not till 6.3 nm) and I will obtain the same value it means that I can decrease
> the pulling distance in future simulations. Am I right?

In theory, as long as you've satisfied yourself that this constitutes a 
sufficient representation of a non-interacting state, or as close to it as one 
can achieve in a system of finite size.  I've already said what I think are 
reasonable criteria for a preliminary assessment; it's up to you to convince 
anyone reading your work that such measurements are sound and appropriate.



Justin A. Lemkul, Ph.D.
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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