[gmx-users] PCA problems

[jkrieger at mrc-lmb.cam.ac.uk]

ok thanks Tsjerk. I think that makes sense now.

Best wishes
James

> Hi James,
>
> That's silly! Ambiguous means that the same structure can have multiple
> solutions in a fit. The fit to a single reference structure (with more
> than
> three atoms) is never ambiguous. Can never, by definition!
>
> Now if you have two reference structures at hand, and they have (quite)
> different structures, then fitting on one may give a different ensemble
> from fitting on the other. The fit is not consistent, and the
> inconsistency
> is worse for flexible molecules. Different ensembles will mean different
> correlations, thus giving different principal components.
>
> Progressive fitting does not solve the problem. In fact, progressive
> fitting _is_ ambiguous. Let's say we have a series of conformations ABCAC.
> Then we  fit C once to B, which was fitted to A, and later we have C
> fitted
> to A, which was fitted to the previous C. Note that in practice the
> situation will be much worse as we can approach a certain configuration
> from many sides. Using B as reference will yield a fit that is different
> from using A as reference, so the structure C will have two different
> orientations in the resulting ensemble. Hence, the fit is ambiguous.
>
> For structured proteins, the difference will not matter much. However, in
> long trajectories there may be an added contribution (drift) of the
> orientation.
>
> Hope it helps,
>
> Tsjerk
>
> On Wed, Jun 8, 2016 at 5:33 PM, <jkrieger at mrc-lmb.cam.ac.uk> wrote:
>
>> Thanks Tsjerk,
>>
>> Isn't the progressive fit supposed to rotate everything back into the
>> same
>> orientation without having to worry about inferring that orientation
>> from
>> a reference structure that doesn't align well? Each configuration should
>> in theory align well to its predecessor all the way back to the starting
>> structure (which is what I'd usually take as a reference anyway).
>>
>> The original note I was thinking of says as follows:
>>
>> '''Before a PCA, all structures should be superimposed onto a common
>> reference
>> structure. This can be problematic for very flexible systems such as
>> peptides,
>> where the fit may be ambiguous, leading to artificial structural
>> transitions. In
>> certain cases, such problems may be alleviated by using a progressive
>> fit,
>> where
>> each structure is superimposed onto the previous one. It is also
>> important
>> to note
>> that when results of different PCAs are to be compared with each other,
>> then
>> each individual PCA should be based on the same reference structure used
>> for
>> superposition.'''
>>
>> Please could you explain further what it is I have misunderstood.
>>
>> Also would you say a progressive fit is a bad idea for more structured
>> proteins?
>>
>> Many thanks
>> James
>>
>> > Hi James,
>> >
>> > 'Spurious alignment' is the dependence of the resulting ensemble on
>> the
>> > reference structure. Unfortunately, that's not solved by a progressive
>> > fit.
>> > Rather, in a progressive fit, the same configuration can have multiple
>> > orientations, based on the previous structures, which is also
>> problematic
>> > when you're trying to understand spatial correlations between atoms
>> within
>> > their reference frame.
>> >
>> > Cheers,
>> >
>> > Tsjerk
>> >
>> > On Wed, Jun 8, 2016 at 9:27 AM, <jkrieger at mrc-lmb.cam.ac.uk> wrote:
>> >
>> >> Dear Teresa,
>> >>
>> >> That sounds like a periodic boundary issue to me. It could be fixed
>> by
>> >> using a tpr instead of a gro as the gmx covar manual says "All
>> >> structures
>> >> are fitted to the structure in the structure file. When this is not a
>> >> run
>> >> input file periodicity will not be taken into account." Alternatively
>> if
>> >> you don't have a tpr you could use gmx trjconv first with -pbc whole
>> or
>> >> -pbc nojump.
>> >>
>> >> I also remember reading (I think it was in the Hayward and de Groot
>> >> review
>> >> 2008) that fitting peptides to a reference structure can cause
>> spurious
>> >> alignments. I don't know if this is also related to what you're
>> seeing
>> >> but
>> >> it might be worth using gmx trjconv again with-fit progressive then
>> use
>> >> -nofit in gmx covar.
>> >>
>> >> Best wishes
>> >> James
>> >>
>> >> > Dear GROMACS community
>> >> >
>> >> > I am trying to complete a PCA analysis of my peptide adsorbed to a
>> >> > surface. However when I use :
>> >> >
>> >> > gmx covar -s trajectory.gro  -f md_golp_vacuo.xtc
>> >> >
>> >> > and select the protein for both the least squares fit and
>> covariance
>> >> > calculation, followed by
>> >> >
>> >> >
>> >> > gmx anaeig -s trajectory.gro -f md_golp_vacuo.trr -filt filter1.gro
>> >> > -first 1 -last 1 -skip 100
>> >> >
>> >> > and I select the peptide for the least squares and covariance
>> >> > calculation
>> >> >
>> >> > My peptide is now broken up into pieces. Is this right?
>> >> >
>> >> >
>> >> >
>> >> > Best
>> >> > Teresa
>> >> > --
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>> >
>> >
>> >
>> > --
>> > Tsjerk A. Wassenaar, Ph.D.
>> > --
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>
>
>
> --
> Tsjerk A. Wassenaar, Ph.D.
> --
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