For clarity let me rephrase my difficulty.
1) We are not able to establish conclusively that: the 2-3 clusters that
agonist form after binding to the protein are from those sampled by the
apo-protein.
2) The agonist bound trajectory has RMSD almost similar to every
representative of the apo-protein (the RMSD values varies between (2.5-5
A). And there is no clear separation just that we can say that 0-100ns is
similar to cluster 1 of apo and 100-200ns is similar to cluster 2 of apo.
Please suggest which type of analysis will help us check and establish
clearly this hypothesis of "conformational selection".
Thank you.
On Wed, Feb 20, 2013 at 2:34 PM, Vaibhav Dixit <vaibhavadixit.gmail.com>wrote:
> 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
>> > > >
>> > > > _______________________________________________
>> > > > 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
>> > >
>> >
>> >
>> >
>> > --
>> > 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
>> > AMBER.ambermd.org
>> > http://lists.ambermd.org/mailman/listinfo/amber
>> >
>> _______________________________________________
>> AMBER mailing list
>> AMBER.ambermd.org
>> http://lists.ambermd.org/mailman/listinfo/amber
>>
>
>
>
> --
> 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
>
--
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
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Wed Feb 20 2013 - 01:30:03 PST
