Hi Dan,
Thanks for your prompt reply. I was worried that this might be the case. :(
When solvating the box, I used a closeness parameter of 0.4. This might
have altered the thermodynamic equilibrium so that it is no longer
favourable for the ligand to remain in the pocket and it thus exits the
binding pocket with the solvent (as the pocket is known to be sub-optimally
hydrated). I will hold the heavy atoms fixed during the equilibrium stage
to try and avoid this.
Thanks for looking into it for me. :)
Best regards,
ET
On 22 February 2013 22:17, Daniel Roe <daniel.r.roe.gmail.com> wrote:
> Hi,
>
> Based on visualization of the files you provided after 'autoimage',
> this is not an imaging issue: the ligand just falls out of the binding
> pocket.
>
> -Dan
>
> On Fri, Feb 22, 2013 at 2:45 PM, ET <sketchfoot.gmail.com> wrote:
> > Hi Dan,
> >
> > I tried doing that on our amber 12 installation. Unfortunately, it did
> not
> > make a difference.
> >
> > best regards,
> > ET
> >
> >
> > On 22 February 2013 20:19, Daniel Roe <daniel.r.roe.gmail.com> wrote:
> >
> >> Hi,
> >>
> >> I recommend trying the 'autoimage' command in cpptraj.
> >>
> >> -Dan
> >>
> >> On Friday, February 22, 2013, ET wrote:
> >>
> >> > Hi all,
> >> > I'm running a long MD simulation of 100ns of a ligand bound to a
> protein
> >> > using amber 10. I turned iwrap=1 to avoid the simulation stalling due
> >> > to precision errors.
> >> >
> >> >
> >> > ##################
> >> > production run infile
> >> > &cntrl
> >> > nstlim=2000000, dt=0.002, ntx=5, irest=1, ntpr=500, ntwr=500,
> ntwx=500,
> >> > temp0=300.0, ntt=1, tautp=2.0, iwrap=1, ig=-1
> >> >
> >> > ntb=2, ntp=1,
> >> >
> >> > ntc=2, ntf=2,
> >> >
> >> > nrespa=1,
> >> > &end
> >> > #################
> >> >
> >> > I ran a quick test measuring the distance from the hydroxyl group of
> the
> >> > ligand which a primary alcohol with a cis-3-4 double bond to Tyr120.
> The
> >> > distances seemed quite large (distance graphs for one of the ligands
> >> > attatched). When I check the trajectories with vmd or chimera, the
> ligand
> >> > does not seem to be behaving properly: either coming out of the
> pocket or
> >> > getting stuck on part of the protein (when visualized with vmd).
> >> >
> >> > I'm pretty sure this is an imaging problem. I have more simulations
> where
> >> > the ligand comes out of the pocket for a some frames then goes back
> in.
> >> the
> >> > larger image enclosed illustrates the issue across 3 repeats of 4
> >> different
> >> > ligands bound to the same protein. Each graph measures distance
> between
> >> the
> >> > ligand and Tyr120 of a different trajectory. The protein MUP is like a
> >> > barrel and the ligand is expected to be relatively mobile within the
> >> > pocket, but prob not to this extent.
> >> >
> >> > I have looked through the archives and tried applying the following
> ptraj
> >> > imaging commands with no success;
> >> >
> >> > The protein residues = 1-157
> >> > The ligand = 158
> >> > #############
> >> > trajin md_1.crd
> >> > center :1-157 mass origin
> >> > image :1-157 origin center bymask :1-157 familiar
> >> > center :1-158 mass origin
> >> > image :1-158 origin center bymask :1-158 familiar
> >> > trajout md_1_manImaged.ncdf netcdf
> >> > #############
> >> >
> >> > Zipped Files containing the first 300 frames of a original (before
> >> imaging)
> >> > trajectory and topology files can be downloaded from the following
> links:
> >> >
> >> > 1) 3c6-ligand-protein:
> >> > https://dl.dropbox.com/u/12686110/04_3c6.zip
> >> >
> >> >
> >> > Any help anyone could offer to solve this issue would be greatly
> >> > appreciated.
> >> >
> >> > Best regards,
> >> > ET
> >> >
> >>
> >>
> >> --
> >> -------------------------
> >> Daniel R. Roe, PhD
> >> Department of Medicinal Chemistry
> >> University of Utah
> >> 30 South 2000 East, Room 201
> >> Salt Lake City, UT 84112-5820
> >> http://home.chpc.utah.edu/~cheatham/
> >> (801) 587-9652
> >> (801) 585-9119 (Fax)
> >> _______________________________________________
> >> AMBER mailing list
> >> AMBER.ambermd.org
> >> http://lists.ambermd.org/mailman/listinfo/amber
> >>
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
>
>
>
> --
> -------------------------
> Daniel R. Roe, PhD
> Department of Medicinal Chemistry
> University of Utah
> 30 South 2000 East, Room 201
> Salt Lake City, UT 84112-5820
> http://home.chpc.utah.edu/~cheatham/
> (801) 587-9652
> (801) 585-9119 (Fax)
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
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Received on Fri Feb 22 2013 - 15:00:02 PST
