[phenixbb] explicit solvent in low resolution refinement
Frank von Delft
frank.vondelft at sgc.ox.ac.uk
Mon Nov 24 23:16:21 PST 2014
Okay, so could one build them and restrain their positions and
occupancies to those of the high res structure?
The point is: if you've seen a 1st shell water in conserved 20
structures, the chances of it not being there are in fact rather slim -
which is the identical assumption we make to justify NCS.
On 25/11/2014 07:11, Pavel Afonine wrote:
> No, this is different. Note: you restrain to high-res structure, not
> add it to the model.
> Pavel
>
> On 11/24/14 10:54 PM, Frank von Delft wrote:
>> 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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>
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