Katherine,

all good questions and all discussed previously on this very discussion
board. My personal opinion did not change much since 2007:

http://www.dl.ac.uk/list-archive-public/ccp4bb/msg19777.html

although I would probably amend couple of minor things. As for riding
hydrogens, take a look at this thread

[log in to unmask]" target="_blank">http:[log in to unmask]

Personally, I am not opposed to depositing riding hydrogens, I just
don't see much utility in it given that they can be easily recreated
(it's doubtful that different algorithms will place them in grossly
different positions).

On the overarching "what-is-the-right-way-to-refine-a-model" issue, I
vote for freedom. In most cases, interested parties can download the
data and calculate the maps (if one is not satisfied with EDS, e.g. to
take into account potential differences in map generation algorithms).
You may choose to interpret the density differently, and this diversity
of opinions is quite healthy. If you decide to interpret this tube-like
density in the active site as tetraethylene glycol - well, it's your
choice. I may think it's more likely to be a bunch of "disordered
waters", if that makes more sense to me. In the end, crystallographic
models represent *reasonable interpretation* of underlying electron
density.

As for (non-structural) biologists misinterpreting deposited models, it
is crystallographer's job to educate them (I personally think refining
one structure should be mandatory for relevant PhD students). With that
said, to understand Dostoevsky, I must either learn Russian or find
myself a translator. What I cannot do is to claim that I understand Dao
De Jing original manuscripts without mastering zhuanshu calligraphy
style.

Cheers,

Ed.

On Tue, 2010-04-13 at 20:40 -0400, SIPPEL,KATHERINE H wrote:
> Dear Crystallographic Community,
>
> Dr. Holton made a comment today that got me thinking on the issue
> of modeling. This has been a hotly debated topic in our own lab
> but I would like to hear the current opinions of the community as
> a whole. It is a question of two parts.
>
> First, what do you think about modeling into regions of poor
> density? Do you (A) model something in as best you can while
> conforming to ideal geometry/chemistry with full disclosure about
> b-factors in the region, (B) reduce the occupancies of the poorly
> modeled loops/side chains, or (C) truncate your model, removing
> loops and side chains from the model at the cost of statistical
> numbers? From a crystallographers point of view we can assess the
> quality of the model and make informed decisions as to what
> conclusions to draw, however most of the greater scientific
> community has no way to judge this. They do not know what a
> b-factor is or where to look for an occupancy. Are we doing a
> disservice to science by emphasizing the minimization of Rwork and
> Rfree over full disclosure of what we can legitimately see?
>
> Secondly, on a similar vein, what is the community's opinion on
> modeling hydrogens? I have read a lot on the subject and can see
> both sides of the argument. From a crystallographer's point of
> view these are very helpful in maintaining geometry and ensuring
> the model makes chemical sense. I can also see the necessity of
> submitting them to the pdb so that the statistics can be
> recreated. On the other hand most biologist has no comprehension
> of the concept of riding hydrogens. They assume that if the
> hydrogen is in the pdb, that the crystallographer saw it and use
> that information to develop experiments.
>
> I realize that I may be kicking a hornet nest here but I would
> genuinely like to know what people think.
>
> Thanks,
>
> Katherine Sippel
>
> SIPPEL,KATHERINE H
> Ph. D. candidate
> Department of Biochemistry and Molecular Biology
> College of Medicine
> University of Florida


--
Edwin Pozharski, PhD, Assistant Professor
University of Maryland, Baltimore
----------------------------------------------
When the Way is forgotten duty and justice appear;
Then knowledge and wisdom are born along with hypocrisy.
When harmonious relationships dissolve then respect and devotion arise;
When a nation falls to chaos then loyalty and patriotism are born.
------------------------------ / Lao Tse /