[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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