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Hi Guenter,<br>
<br>
while I clearly understand your motivations, I don't feel very
comfortable with placing explicit atoms that are not supported by
the data. <br>
<br>
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.<br>
<br>
All the best,<br>
Pavel<br>
<br>
<div class="moz-cite-prefix">On 11/17/14 1:33 AM, Guenter Fritz
wrote:<br>
</div>
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<div class="moz-cite-prefix">Dear Pavel,<br>
<br>
yes, such an exact prediction of ordered water molecules might
be very helpful. I was sure that somebody else had this idea
already. <br>
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:<br>
<br>
Lunin, V.Y., Afonine, P. & Urzhumtsev, A.G. (2002)
"Likelihood-based refinement. 1. Irremovable model errors.".
Acta Cryst., A58, 270-282. <br>
<br>
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:<br>
<br>
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. <br>
<br>
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. <br>
<br>
Best wishes, Guenter<br>
<br>
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<blockquote cite="mid:546928AF.5090206@lbl.gov" type="cite">
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Hello,<br>
<br>
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).<br>
<br>
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!<br>
<br>
All the best,<br>
Pavel<br>
<br>
<div class="moz-cite-prefix">On 11/16/14 2:19 PM, Nathaniel
Echols wrote:<br>
</div>
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cite="mid:CALeAa1M3mUeYcWEYNEBjtCt21UcSExt+o-j8P-mnDXOsUtN+YQ@mail.gmail.com"
type="cite">
<div dir="ltr">I will leave it to others to debate the wisdom
of this strategy, but to answer the purely technical
question:
<div class="gmail_extra"><br>
<div class="gmail_quote">On Sun, Nov 16, 2014 at 2:06 PM,
Guenter Fritz <span dir="ltr"><<a
moz-do-not-send="true"
href="mailto:guenter.fritz@uni-konstanz.de"
target="_blank">guenter.fritz@uni-konstanz.de</a>></span>
wrote:<br>
<blockquote class="gmail_quote" style="margin:0 0 0
.8ex;border-left:1px #ccc solid;padding-left:1ex">Is
it possible to use protein and water atoms from the
reference models to generate restraints for the low
resolution refinement?<br>
</blockquote>
<div><br>
</div>
<div>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).</div>
<div><br>
</div>
<div>-Nat<br>
</div>
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