Obviously, this depends a bit on which refinement program you use, and I am
not familiar with all of them. However, I have had some conversations with
Garib "refmac" Murshudov and Pavel "phenix.refine" Afonine about this, and the
shocking answer appears to be "no". Carbon has six electrons, even if it is a
methyl carbon with three unmodeled hydrogens stuck to it. Yes, this does
introduce a 33% error in the number of electrons at every CH3! I am also
suspicious that free ions like "Cl" are often modeled as free elemental Cl,
and not the Cl- ion, which has 1 more electron. But this is only a 3% error.
Personally, I think that "something should be done" about disordered aliphatic
hydrogens (particularly since I don't have to code it). I suggest that simply
adding "3" to the "constant" coefficient of the "C" form factor to make a "CH3
form factor" might just do the trick. Not only are the electrons brought in
by the H atoms generally delocalized into the carbon's electron cloud anyway,
but at most MX resolutions, the whole CH3 group is just one big fat lump of 9
electrons. Mathematically, this is equivalent to saying that the B-factor
Gaussian (1.5 A FWHM when B=30) dominates the 5 much narrower Gaussians of the
atomic form factor.
That said, I should also add that our illustrious refinement program authors
have good reasons for doing things the way they do. Mostly because users can
say some very unkind things if the new version makes their R factors go up.
It is true that riding hydrogens "count" as one electron each, but it is not
always clear where to put them, and in situations like methyl group hydrogens
they could be anywhere in the "doughnut of uncertainty" traced out by rotating
the X-CH3 about its X-C bond. It is tempting to say that this doughnut should
be modeled in somehow, but an important caveat to remember is that putting an
atom in the wrong place is twice as bad as leaving it out. That is, you get
one difference feature if the atom is missing, but two (one positive, one
negative) if it is wrong. So, a "doughnut atom" is expected to at best cancel
itself out. One could call this a corollary of of the general principles of
model building: "When it doubt, don't".
But what about MolProbity? and all those neat inter-digitating hydrogens?
Should it not be possible for the refinement program to be "smarter" about
where it puts riding hydrogens? Well, that is always possible, but I don't
think MolProbity is exactly built into refmac. You can, however, run
MolProbity before you put your model into refinement!
The problem, of course, is if you have a 4.5 A structure with all the
hydrogens built in you will get hateful comments containing the word
"parameters" from undereducated reviewers. I say "undereducated" because
getting the electron count right is actually MORE important for low-angle
structure factors than it is for high-angle ones (the extreme case of this
being F000 itself). Yes, explicit hydrogen atoms do slow down the refinement,
and clutter the graphics, but they do not really add much by way of "free
parameters". Not if the geometric restraints are sensible. In fact, the
central lesson of MolProbity is that hydrogens do introduce (at least
potentially) better geometric restraints. Sort of like what an elastic
network model can do (ahem).
-James Holton
MAD Scientist
On 1/6/2011 8:15 PM, Kenneth A. Satyshur wrote:
Persons of interest:
I understood that refinements in refmac of low res structures without
hydrogens includes a component of the Hydrogen atom attached to the
carbon in the carbon scattering factors. Or is this just if the Hydrogen
atoms
are in the riding position. If so, why bother to add hydrogens in the
riding
position.
Thanks
kas
--
Kenneth A. Satyshur, M.S.,Ph.D.
Associate Scientist
University of Wisconsin
Madison, Wisconsin 53706
608-215-5207
