[phenixbb] explicit solvent in low resolution refinement
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
>> 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,
>> 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
>>> 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
>>>> 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,
>>>> 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
>>>>> 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).
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