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
> >
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
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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
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Received on Thu Oct 18 2012 - 08:00:03 PDT
