[phenixbb] explicit solvent in low resolution refinement

Pavel Afonine pafonine at lbl.gov
Mon Nov 24 23:11:42 PST 2014

No, this is different. Note: you restrain to high-res structure, not add 
it to the model.

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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