[gmx-users] Calculating the distance between protein and ligand during ligand diffusion out of the box

[bipin singh]

Thanks for the reply Dr. Trayder and Dr. Justin.

I have performed unrestrained MD with a ligand bound protein having surface
exposed binding pocket (link of the image attached for clarification). I
have used a cubic box with vectors 6.432nm and the system size was 4.117
3.878 and 4.059 (in nm).

http://researchweb.iiit.ac.in/~bipin.singh/snapshot.png

My doubt is how to discriminate between a real ligand binding/unbinding
process and the rebinding observed due to PBC effects (i.e. when ligand
diffuses out the box and a subsequent another ligand comes and bind from
the adjacent periodic image, which may seen as a rebinding event during
distance calculation).

On Tue, Oct 8, 2013 at 6:37 AM, Trayder Thomas <trayder.thomas at monash.edu>wrote:

> With a ligand diffusing as freely as I'm assuming (you've omitted a lot of
> info, box size etc.) you aren't going to get PBC to play nice, although
> -nojump should have atleast given you a different wrong answer.
>
> Centering the system on the same point you are using to define the binding
> pocket (may require custom index groups) should get you something more
> reasonable looking.
>
> Also, it depends on the size of your protein and what you're doing but you
> should consider if it's even relevant whether the ligand is 2nm away or 5?
>
> -Trayder
>
>
>
> On Tue, Oct 8, 2013 at 6:53 AM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
> >
> >
> > On 10/7/13 1:39 PM, bipin singh wrote:
> >
> >> Thanks for the reply Dr. Justin.
> >> I have also thinking of the same possibility but to further confirm, I
> am
> >> sending the link for the plot of the distance between the COM of ligand
> >> binding pocket and COM of ligand molecule, please find some time to
> have a
> >> look at the plot and let me know if it seems a feasible behaviour
> during a
> >> simulation.
> >>
> >> http://researchweb.iiit.ac.in/**~bipin.singh/plot.png<
> http://researchweb.iiit.ac.in/~bipin.singh/plot.png>
> >>
> >>
> > Looks like nothing more than random motion to me.  Since you haven't told
> > us what you're doing (unrestrained MD? pulling?), it's hard to comment
> > further.
> >
> > -Justin
> >
> >
> >  On Mon, Oct 7, 2013 at 8:22 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
> >>
> >>
> >>>
> >>> On 10/7/13 10:46 AM, bipin singh wrote:
> >>>
> >>>  Hello All,
> >>>>
> >>>> I have calculated the distance between the binding pocket of protein
> and
> >>>> the ligand molecule but due to ligand diffusion out of box, I am
> getting
> >>>> wrong distance as first it increases till 5nm and then decrease again
> to
> >>>> around 1nm during the simulation (which is not possible).
> >>>>
> >>>> I have fitted my trajectory with using trjconv -pbc mol -ur compact
> >>>> -center
> >>>> (protein) option.
> >>>>
> >>>> I have also tried the -nojump option but getting the same results for
> >>>> distances.
> >>>>
> >>>> Please suggest how to get the real distance without the PBC effect.
> >>>>
> >>>>
> >>>>  It sounds like that very well could be the real distance.  If the
> >>> ligand
> >>> diffused out, it simply becomes part of the solvent around the protein
> >>> and
> >>> can diffuse around freely.
> >>>
> >>> -Justin
> >>>
> >>> --
> >>> ==============================****====================
> >>>
> >>> Justin A. Lemkul, Ph.D.
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> >
> > Justin A. Lemkul, Ph.D.
> > Postdoctoral Fellow
> >
> > Department of Pharmaceutical Sciences
> > School of Pharmacy
> > Health Sciences Facility II, Room 601
> > University of Maryland, Baltimore
> > 20 Penn St.
> > Baltimore, MD 21201
> >
> > jalemkul at outerbanks.umaryland.**edu <jalemkul at outerbanks.umaryland.edu>
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-- 
*-----------------------
Thanks and Regards,
Bipin Singh*