[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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