On Tuesday, 20 December 2016 10:28:44 PM Pavel Afonine wrote:
> Hi Dirk,
>
>
> I want to check the validity of the refinement of anisotropic B-factors vs.
> > TLS + isototropic B-factors using the Hamilton R-value ratio test as
> > described in Ethan Merritt's paper "To B or not to B", Acta Cryst. D, Vol
> > 68, pp 468. This test uses the generalised R-factors (assuming unit
> > weights), RG=(Sum(Fo-Fc)^2/Sum(Fo)^2)^1/2. Although Hamilton wrote that
> > at the end of refinement, one could also use the similar ratio of the usual
> > R-factors, I really would like to check the ratio of the RG-values after
> > refinement. As far as I can see, this value is not reported by the usual
> > refinement programs.
>
>
>
> R factor is a global metric that, if considered alone, is not going to
> answer your question. Best is to consider all three:
>
> 1) Rfree;
> 2) Rfree-Rwork;
> 3) Meaningfulness of refined TLS matrices. Note, as we discovered and
> documented recently, results of TLS refinements (TLS matrices) are
> nonsensical in 85% of PDB entries (yes, eighty-five are bad, believe it or
> not!):
> From deep TLS validation to ensembles of atomic models built from elemental
> motions. A. Urzhumtsev, P. V. Afonine, A. H. Van Benschoten, J. S. Fraser and
> P. D.
> Adams. Acta Cryst. (2015). D71, 1668-1683.
As you know, I disagree on this point.
The Urzhumtsev et al classification of "nonsensical" TLS matrices includes
many that make lots of sense but do not happen to describe a perfectly rigid
body.
That's OK, because proteins are not perfectly rigid bodies.
The TLS models are useful approximations that capture
essential features of a messy ensemble of protein atoms.
Complaining that in practice the refined TLS values deviate from those that
would hypothetically be obtained from fitting perfectly rigid groups is beside
the point.
Of course some refinements really are bad and some models really are
unreasonable. Validation tests can help you catch these and fix your
model or refinement. But a validation criterion that is so strict that
it labels 85% of all protein refinements as "nonsensical" is not a very
useful test.
>
> I'd say if you pass "1-3)" you are more than good. If still in doubt, you
> can make an extra effort and do what's described in
>
> Validation of crystallographic models containing TLS or other descriptions
> of anisotropy
> F. Zucker, P. C. Champ and E. A. Merritt
> Acta Cryst. (2010). D66, 889-900
>
> which may reveal extra troubles.
Note that the primary validation test described in the Zucker paper
(we called it SKITTLS) is a check for the pairwise consistency of
adjacent TLS groups. It might flag as inconsistent two adjacent
groups that both pass the criteria in Urzhumtsev et al, or conversely
it might rate two groups that fail the Urzhumtsev criteria as being
nevertheless consistent in their description of atoms they jointly
apply to.
Ethan
> All the best,
> Pavel
--
Ethan A Merritt, Dept of Biochemistry
Biomolecular Structure Center, K-428 Health Sciences Bldg
MS 357742, University of Washington, Seattle 98195-7742
