Dear Amber users and Prof. C. Simmerling,
Based on the clustering analysis with the option "epsilon 2.1" we have
results that apo-protein form 5 clusters, and other agonist bound ligands
for 2-3 clusters. But we are having difficulty in establishing the fact
that these 2-3 clusters from from the 5 cluster sampled by the apo-protein.
RMSD of representative structures is not conclusively establishing this
fact.
We also tried cpptraj to plot the rmsd of each (agonist bound) trajectory
using representatives of the apo-protein as reference (with appropriate
mask), but that also is not helpful in supporting the hypothesis. The
ligand bound trajectory has also similar rmsd against the representative of
apo-protein (between 2-5 A).
Please suggest how else can we test this hypothesis?
Thanks in advance for your suggestions.
On Thu, Oct 18, 2012 at 8:22 PM, Carlos Simmerling <
carlos.simmerling.gmail.com> wrote:
> this sounds good, let us know if you run into problems.
>
>
> On Thu, Oct 18, 2012 at 10:37 AM, vaibhav dixit <vaibhavadixit.gmail.com
> >wrote:
>
> > Dear Amber community members,
> > Please suggest on the following. Am I doing the right analysis?
> > In the case that I'm applying clustering to, there is an apo-protein
> which
> > samples 5 different dominant conformations.
> > But when the ligand is bound, it appears that, out of the five only 2-3
> > conformations are sampled and remain dominant. This is because of the
> > stabilization of selected states by the ligand.
> >
> > In such a situation, earlier I tried to use average PDBs for analysis.
> But
> > once I realized that there are usual bonds and the structure is not
> > chemically meaningful, I shifted my focus towards the representative
> > structures given by the clustering algorithm.
> > Thus I'm now analyzing RMSD within and between the clusters of various
> > complexes using the representative structures.
> >
> > Please suggest if this approach is good and how can I use the average
> PDBs
> > in my analysis. I guess they are not good for RMSD analysis, are they?
> >
> > Thanks in advance.
> >
> > On Thu, Oct 18, 2012 at 7:54 PM, Carlos Simmerling <
> > carlos.simmerling.gmail.com> wrote:
> >
> > > I second what Jason said about using the representative structure from
> > > clustering. If the average structure is distorted, then minimizing it
> > will
> > > give good geometries but this can suggest that the ensemble looks like
> > the
> > > minimized average, which it doesn't. With distortions at least people
> are
> > > aware that there is some diversity. Artificially getting rid of it can
> be
> > > very misleading. For example, if you have 2 alternate conformations,
> and
> > > the average is distorted as a result, minimizing it will make it look
> to
> > > your audience like you only have 1 dominant conformation, and even
> worse,
> > > it might not look like any of the actual clusters at all. I would only
> > use
> > > the minimized average if you have strong evidence that there is a
> single
> > > dominant cluster with small fluctuations about the average.
> > >
> > >
> > > On Thu, Oct 18, 2012 at 10:09 AM, <steinbrt.rci.rutgers.edu> wrote:
> > >
> > > > Hi Mu,
> > > >
> > > > Jason is absolutely correct here, but for the sake of prettier
> > > > presentations, it is common to take the average structure that amber
> > > gives
> > > > you and conduct a short energy minimization of it. This should give
> > you a
> > > > chemically normal-looking structure that is at least somewhat close
> to
> > > the
> > > > average one. Alternatively, you would pick and show the snapshot from
> > > your
> > > > MD that has the lowest rmsd compared to the average one. I find that
> to
> > > be
> > > > a good compromise between the true average and a model that people
> can
> > > > make sense of.
> > > >
> > > > Thomas
> > > >
> > > > On Thu, October 18, 2012 9:44 am, Jason Swails wrote:
> > > > > On Thu, Oct 18, 2012 at 5:40 AM, Mu Xia <muxiachuixue.163.com>
> > wrote:
> > > > >
> > > > >> Hi all,
> > > > >>
> > > > >>
> > > > >> I want to get an average structure of the ligand-protein complex
> > from
> > > > >> the
> > > > >> trajectories generated by MD. So I use the ptraj command. The
> input
> > > file
> > > > >> is
> > > > >> as following.
> > > > >>
> > > > >>
> > > > >> trajin production1.mdcrd
> > > > >> rms first mass .CA,C,N
> > > > >> average a.pdb pdb
> > > > >>
> > > > >>
> > > > >> When examining a.pdb in VMD, I find that the X-H (X is the heavy
> > atom)
> > > > >> bonds are abnormally short.
> > > > >>
> > > > >
> > > > > This makes sense. H atoms typically rotate fairly freely (they are
> > > small
> > > > > and there is little steric hindrance in many instances to free
> > > rotation).
> > > > > Also, for groups like CH3, the 3 hydrogens are, at least
> > approximately,
> > > > > rotationally degenerate, meaning they should have approximately the
> > > same
> > > > > average location (which will be nearly on top of the heteroatom).
> > > > >
> > > > >
> > > > >> My question is, how could I get a correct average structure
> > containing
> > > > >> normal bonds and coordinates?
> > > > >>
> > > > >
> > > > > What you got *is* a correct average structure (i.e., it is *the*
> > > average
> > > > > structure). "Normal bonds and coordinates" would be something you
> > > would
> > > > > find in a 'representative structure' in cluster analysis or
> something
> > > of
> > > > > the like.
> > > > >
> > > > > HTH,
> > > > > Jason
> > > > >
> > > > > --
> > > > > Jason M. Swails
> > > > > Quantum Theory Project,
> > > > > University of Florida
> > > > > Ph.D. Candidate
> > > > > 352-392-4032
> > > > > _______________________________________________
> > > > > AMBER mailing list
> > > > > AMBER.ambermd.org
> > > > > http://lists.ambermd.org/mailman/listinfo/amber
> > > > >
> > > >
> > > >
> > > > Dr. Thomas Steinbrecher
> > > > formerly at the
> > > > BioMaps Institute
> > > > Rutgers University
> > > > 610 Taylor Rd.
> > > > Piscataway, NJ 08854
> > > >
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> > > >
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> > >
> >
> >
> >
> > --
> > With regards
> >
> > Vaibhav A. Dixit
> > Ph.D. Scholar
> > Department of Medicinal Chemistry
> > Natl. Inst. Pharm. Edu. & Res. (NIPER)
> > Sector 67, Phase X, S.A.S. Nagar (Mohali)
> > Punjab -160 062 INDIA
> > Phone (Mobile): +919915214408
> > E-mail: vaibhavadixit.gmail.com
> > www.niper.nic.in
> > _______________________________________________
> > AMBER mailing list
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> >
> _______________________________________________
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>
--
With regards
Vaibhav A. Dixit
Ph.D.
Department of Medicinal Chemistry
Natl. Inst. Pharm. Edu. & Res. (NIPER)
Sector 67, Phase X, S.A.S. Nagar (Mohali)
Punjab -160 062 INDIA
Phone (Mobile): +919915214408, +91-7709129400.
E-mail: vaibhavadixit.gmail.com
www.niper.nic.in
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Received on Wed Feb 20 2013 - 01:30:03 PST
