[gmx-users] PCA problems

[Antonio Baptista]

Hi James,

If your molecule shows some flexiblility, I would suggest using as a 
reference the structure of your original ensemble that produces the fitted 
ensemble with the lowest sum of RMSD values to that structure (or their 
square). That usually gives a fitted ensemble that more closely retains 
the original RMSD values between all pairs of structures.

If your molecule is well-structured, it wouldn't make much difference 
which reference you use, as Tsjerk said.

Best,
Antonio


On Wed, 8 Jun 2016, jkrieger at mrc-lmb.cam.ac.uk wrote:

> 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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>>
>>
>> --
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