[phenixbb] explicit solvent in low resolution refinement
Frank von Delft
frank.vondelft at sgc.ox.ac.uk
Mon Nov 24 22:54:40 PST 2014
Well, we happily restrain (these days) low resolution structures to high
resolution structures. I see no philosophical difference.
On 25/11/2014 05:58, Pavel Afonine wrote:
> Hi Guenter,
>
> while I clearly understand your motivations, I don't feel very
> comfortable with placing explicit atoms that are not supported by the
> data.
>
> The fact that those atoms are present in high-resolution structure
> does not mean that they are also present in low-resolution structure.
> You can argue that adding these waters improves Rfree and you may
> think of it as an improvement. However, as a counterargument one can
> say that R-factor is a global metric that is unlikely to be sensitive
> to adding/removing just one single molecule. Therefore, while adding
> bulk of "structured" waters may be an improvement in general this
> still does not mean that all the waters you add are true and good
> ones. Say what if 70% of them are good and 30% are rubbish? In this
> case still Rfree may improve because you add more good water than bad,
> but adding bad ones is counterproductive anyway and introduces model
> bias and thus must be avoided.
>
> All the best,
> Pavel
>
> On 11/17/14 1:33 AM, Guenter Fritz wrote:
>> Dear Pavel,
>>
>> yes, such an exact prediction of ordered water molecules might be
>> very helpful. I was sure that somebody else had this idea already.
>> I was playing around with a few datasets truncated a low resolution
>> (3.5 - 4.0 A) and then compared Rwork/Rfree using an input model with
>> and without water molecules. Clearly the water molecules had a large
>> contribution in the refinement of these artificially truncated
>> datasets. Sascha pointed me to an example in your paper from 2002:
>>
>> Lunin, V.Y., Afonine, P. & Urzhumtsev, A.G. (2002) "Likelihood-based
>> refinement. 1. Irremovable model errors.". Acta Cryst., A58, 270-282.
>>
>> I had a look into the literature to get an idea and found several
>> programs evaluating the inner shell water molecules and some programs
>> predicting water positions. I had a try only on a few programs. I
>> found that a nice summary is given in the publication on an approach
>> called WaterDock:
>>
>> Ross GA, Morris GM, Biggin PC (2012) "Rapid and accurate prediction
>> and scoring of water molecules in protein binding sites." PLoS One
>> 7(3):e32036.
>>
>> But before analyzing many structures and see whether it might work in
>> general, my aim is much simpler. I have high resolution structures
>> of with water molecules and try to implement the ordered water
>> molecules into the refinement of a protein complex at low resolution.
>> My approach was maybe a bit of naive so far but I am sure there is
>> good way to do that.
>>
>> Best wishes, Guenter
>>
>>> Hello,
>>>
>>> I tried this idea back in 2004. In a nutshell: using all (or
>>> categorized subset of) structures in PDB we can learn about
>>> distribution of structured water and given this knowledge we can
>>> build an a priori contribution of scattering arising from such water
>>> to the scattering of any given new structure or a structure at low
>>> resolution (where the water is not visible in maps).
>>>
>>> Either I did not spend enough time on this or the idea wasn't
>>> viable, but one way or another this did not work in my hands. I
>>> think it may be worth revisiting this 10 years later! Perhaps I
>>> would do it better now than back then!
>>>
>>> All the best,
>>> Pavel
>>>
>>> On 11/16/14 2:19 PM, Nathaniel Echols wrote:
>>>> I will leave it to others to debate the wisdom of this strategy,
>>>> but to answer the purely technical question:
>>>>
>>>> On Sun, Nov 16, 2014 at 2:06 PM, Guenter Fritz
>>>> <guenter.fritz at uni-konstanz.de
>>>> <mailto:guenter.fritz at uni-konstanz.de>> wrote:
>>>>
>>>> Is it possible to use protein and water atoms from the
>>>> reference models to generate restraints for the low resolution
>>>> refinement?
>>>>
>>>>
>>>> I don't think so. You'll probably find it easier to refine the
>>>> atoms separately, i.e. one run with reference model and the
>>>> individual sites selection set to "not resname HOH", followed by a
>>>> run with harmonic restraints on waters and selection "resname
>>>> HOH". Alternately, you could try applying harmonic restraints to
>>>> the entire model, although I suspect that the waters and protein
>>>> require different weights (or sigmas).
>>>>
>>>> -Nat
>
>
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