[phenixbb] explicit solvent in low resolution refinement

Guenter Fritz guenter.fritz at uni-konstanz.de
Mon Nov 17 01:33:18 PST 2014


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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