[gmx-users] PMF profile from Umbrella - Plateau

[Steven Neumann]

On Wed, May 16, 2012 at 4:20 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:

>
>
> 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


Thanks. Well, as my cutoff is 1.4 nm pulling 3.5 nm will suffice - and
having the same value in the example makes reasonable argument for pulling
e.g. 4nm to be on the safe side.

Steven


>
>
> --
> ==============================**==========
>
> Justin A. Lemkul, Ph.D.
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
>
> ==============================**==========
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