[gmx-users] Validation of molecular dynamic simulation results

Tue Feb 11 15:05:35 CET 2014

Hi Ananya,

You have several options to validate the results you have

1. Perform the simulations again
2. Apply the reverse mutations and simulate again
3. Perform (covariance) analysis on different blocks
4. Extract a measurable property and compare it to experiments

ad 1.:

Redoing the simulations is pretty trivial. Just set different initial
velocities, different random placement of ions. If the results end up the
same, that gives confidence that your approach is solid.

ad 2.:

If the effect you see is due to the mutation, then reversing the mutation
should bring you in the opposite direction again.

ad 3.:

If you've reached an equilibrium situation, then your principal components
will end up the same AND the mean projections per window will be
approximately equal.

ad 4.:

If there's anything known about NOEs obtained from NMR or the hydrodynamic
radius or something else from experiments, you can derive related
properties from your simulations and compare these (qualitatively,
probably).

Hope it helps,

Tsjerk

On Tue, Feb 11, 2014 at 1:38 PM, João Henriques <
joao.henriques.32353 at gmail.com> wrote:

> First of all, please address me in a casual manner, "Sir" makes me feel old
> and I'm just in my mid 20's :)
>
> Now I'll try to be as less verbose as I can, because I think there's a
> little communication issue here.
>
> Authenticity usually points out towards originality, something not copied,
> genuine. I knew you meant something different and thus my previous remark.
>
> You don't have to tell us the full story behind the study you're doing.
> This mailing list serves to help people with difficulties regarding the
> gromacs software package. Your difficulty lies elsewhere, ie. you want
> someone to tell you what to do next in your project. *That is a scientific
> decision not a technical issue*, if you understand what I mean. It's
> something you have to discuss with your research group and
> collaborators. Unless you come to me with a concrete idea for an
> analysis/study I'm afraid I can't help you.
>
> Don't take this personally, but I simply can not do your "homework" in
> full. *Come to me with a concrete idea like, "I want to measure how
> dissimilar A and B are" or "I want to know how I can compute this and
> that", etc, and then I (or someone else) might be able to assist you.*
>
> Best regards,
> João
>
>
>
> On Tue, Feb 11, 2014 at 12:43 PM, ananyachatterjee <
> ananyachatterjee at iiserkol.ac.in> wrote:
>
> > Dear Sir,
> >
> > My protein contains two domain and upon GTP hydrolysis, the protein under
> > goes conformational change and it shows inter-domain movement. I did few
> > biochemical test which showed me that the upon a mutation in the
> conserved
> > residue (which is localed in the chain connecting the two domain)the
> GTPase
> > activity is reduced and also it has effected the cell growth. Now to see
> > whether the mutation is some how effecting the inter domain movement of
> the
> > protein(which is a important property of the protein for it function) I
> > performed the simulations keeping the parameters close to the biochemical
> > experiments(like con. of ions, temp. etc) . Now when I presented my work
> in
> > a conference people asked me about its authenticity, how much close it is
> > to the reality and whether it is reproducible. I want to know how to
> verify
> > my simulations.
> >
> > Thanks in advance
> >
> >
> > On Tue, 11 Feb 2014 11:24:53 +0100, João Henriques wrote:
> >
> >> Dear Ananya,
> >>
> >> Sorry but I don't understand what you're saying. What do you mean by
> >> "molecular
> >> movement of my protein"? Do you mean diffusion? Please be more specific.
> >> You also mention "authenticity", but I don't think that's what you
> >> meant...
> >>
> >> You have done PCA, RMSD and RMSF analyses. That's nice and all, but do
> you
> >> have a reason for doing them? What I meant with my previous email is
> >> that *there
> >>
> >> is no fixed recipe that one must always follow in order to validate
> their
> >> simulations*. The analyses your simulation requires in order to be
> >>
> >> validated depend on the simulation purpose and what experimental data
> you
> >> have to compare them to.
> >>
> >> Take this overly simplistic example: Imagine I've performed a simple
> >> "protein in water" MD simulation. The protein is well behaved (stable
> >> native structure) and there is a high resolution experimental structure
> of
> >> it. Radius of gyration, RMSD, RMSF and DSSP analyses would be good
> >> candidates to show whether my force field, settings and parameters are
> >> adequate or not in maintaining the well known native 3D structure.
> >>
> >> Like I said before, you're the one that must be familiar with your
> system,
> >> simulation and overall project aim. I am happy to help you in
> identifying
> >> the tool you need to perform a certain analysis/study or even helping
> >> understanding any error or problem with it. However I cannot do your own
> >> work in identifying what needs to be done and where you're heading.
> >>
> >> Best regards,
> >> João
> >>
> >>
> >> On Tue, Feb 11, 2014 at 9:46 AM, ananyachatterjee <
> >> ananyachatterjee at iiserkol.ac.in> wrote:
> >>
> >>  On Tue, 11 Feb 2014 09:05:19 +0100, João Henriques wrote:
> >>>
> >>>  Dear Ananya,
> >>>>
> >>>> Shouldn't this be something you already had in mind even before
> >>>> attempting
> >>>> to simulate? Usually, a simulation is a means to an end. What is your
> >>>> end,
> >>>> ie. what made you do this simulation? The motivation behind your
> >>>> simulation
> >>>> is usually what will determine what type of validation it requires.
> >>>> Sure,
> >>>> there are quasi-standard analysis and sanity checks that one almost
> >>>> always
> >>>> uses to ensure the simulation is relevant, but you can find those in
> any
> >>>> given MD tutorial available online. For this, Google is your friend
> and
> >>>> you
> >>>> also have quite popular tutorials such as Justin's for example:
> >>>>
> >>>>
> >>>>
> >>>>
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/
> >>>>
> >>>> I suggest you sit down and think a bit about what are you attempting
> to
> >>>> achieve with your simulation. Pinpoint what type of analysis you need
> >>>> and
> >>>> then take a careful look at the Gromacs manual. There you will find
> all
> >>>> you
> >>>> need to know about the analysis tools available to you. They're not
> >>>> guaranteed to cover all your needs, but they usually more than suffice
> >>>> in
> >>>> providing what most researchers need to validate their simulations.
> >>>>
> >>>> Best regards,
> >>>> João
> >>>>
> >>>>
> >>>> On Tue, Feb 11, 2014 at 8:02 AM, ananyachatterjee <
> >>>> ananyachatterjee at iiserkol.ac.in> wrote:
> >>>>
> >>>>  Hello everyone,
> >>>>
> >>>>>
> >>>>> I have done a set of molecular dynamic simulation of my protein and
> its
> >>>>> mutated structure, now please tell me how should I validate the
> >>>>> simulation
> >>>>> results or structures. Whether I can reproduce the same simulations.
> >>>>>
> >>>>> Thank you in advance
> >>>>>
> >>>>> --
> >>>>> Ananya Chatterjee,
> >>>>> Senior Research Fellow (SRF),
> >>>>> Department of biological Science,
> >>>>> IISER-Kolkata.
> >>>>> --
> >>>>> Gromacs Users mailing list
> >>>>>
> >>>>> * Please search the archive at http://www.gromacs.org/
> >>>>> Support/Mailing_Lists/GMX-Users_List before posting!
> >>>>>
> >>>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
> >>>>>
> >>>>> * For (un)subscribe requests visit
> >>>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-usersor
> >>>>> send a mail to gmx-users-request at gromacs.org.
> >>>>>
> >>>>>
> >>>>>  Dear João,
> >>>
> >>> Thank you for your reply, I was intended to seen the difference in
> >>> molecular movement of my protein upon mutation. My protein is a GTPase
> >>> protein and I have done simulation in presence of GTP, GDP and GDP+Pi
> for
> >>> both the wild type and the mutated protein. Then I have done principle
> >>> component analysis and RMSD & RMSF comparison of the trajectories. Now
> I
> >>> want to check the authenticity of the set of simulation and whether
> they
> >>> can be reproduce to validate my results.
> >>>
> >>> Please kindly help me in this regard.
> >>>
> >>> --
> >>> Ananya Chatterjee,
> >>> Senior Research Fellow (SRF),
> >>> Department of biological Science,
> >>> IISER-Kolkata.
> >>> --
> >>> Gromacs Users mailing list
> >>>
> >>> * Please search the archive at http://www.gromacs.org/
> >>> Support/Mailing_Lists/GMX-Users_List before posting!
> >>>
> >>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
> >>>
> >>> * For (un)subscribe requests visit
> >>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
> >>> send a mail to gmx-users-request at gromacs.org.
> >>>
> >>>
> > --
> > Ananya Chatterjee,
> > Senior Research Fellow (SRF),
> > Department of biological Science,
> > IISER-Kolkata.
> > --
> > Gromacs Users mailing list
> >
> > * Please search the archive at http://www.gromacs.org/
> > Support/Mailing_Lists/GMX-Users_List before posting!
> >
> > * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
> >
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> >
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-- 
Tsjerk A. Wassenaar, Ph.D.