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

Trayder Thomas trayder.thomas at monash.edu
Tue Oct 8 08:27:15 CEST 2013


Both cases are 'real' ligand binding. If a drug binds, it binds. It doesn't
matter how far away it comes from.
Each periodic image is identical, it's the same ligand capable of making
the same interactions in the same protein but approaching from a different
angle.

-Trayder


On Tue, Oct 8, 2013 at 4:07 PM, bipin singh <bipinelmat at gmail.com> wrote:

> 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.
> > >>> Postdoctoral Fellow
> > >>>
> > >>> Department of Pharmaceutical Sciences
> > >>> School of Pharmacy
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> > >>> University of Maryland, Baltimore
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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.
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> >
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> --
> *-----------------------
> Thanks and Regards,
> Bipin Singh*
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