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 <[email protected]> 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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