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
