RE: [ccp4bb]: refinement weights

["Gerard \"DVD\" Kleywegt" <gerard@xray.bmc.uu.se>]

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> 1.5-2.0 degrees. Regarding the doubling of the wa in CNS: if you look at the
> scalenbulk module, which determines that weight, the refined wa is divided
> by a factor of 2. This factor was introduced later (as Paul Adams told me),
> but I always remove it, because otherwise CNS refines the model with, in my
> experience, too tightly restrained geometry.

i suspect this is the factor two that goes back to the early days of Rfree,
when many people playing around with WA in Xplor found that taking 1/3 or 1/2
of the WA value recommended by Xplor itself tended to give the lowest Rfree
values (using simulated-annealing refinement).

i would like to caution against letting "experience" or "validation programs"
talking you into increasing WA mindlessly. unless you have very high
resolution data, you should restrain your geometry tightly (how tightly ? ask
Ms R Free).

dictionaries have target values and ESDs for bond lengths, angles, etc., but
you should remember that these ESDs are calculated for a population of
very-high-resolution small-molecule structures. there is *no reason
whatsoever* for you to expect the combined bond lengths and angles in your 4
A, 3 A, or even 2 A model to reproduce the ESDs of that very special
population. of course, you can always relax the weight on the stereochemical
restraints and obtain just about *any* ESD you like. *however*, you should
remember that "where freedom is given, liberties are taken" - the extra slack
you are cutting the geometry is likely to be distributed randomly (or rather,
in such a way as to enable the largest drop in value of the refinement's
target function). if Rfree tells you that this is a great thing to do - fine.
if not, leave WA alone.

some pointers for the youngsters and/or novices:

- Kleywegt, G.J. and Jones, T.A. (1995). Where freedom is given, liberties are
  taken. Structure 3, 535-540.

- Kleywegt, G.J. and Brunger, A.T. (1996). Checking your imagination:
  applications of the free R value. Structure 4, 897-904. (and references
  therein)

- model-building and refinement practice:
  http://xray.bmc.uu.se/gerard/gmrp/gmrp.html

- a crystallographer's guide to interpreting WHATIF output:
  http://xray.bmc.uu.se/usf/whatif.html

- validation tutorial: http://xray.bmc.uu.se/gerard/embo2001/modval/index.html


--dvd

******************************************************************
                        Gerard J.  Kleywegt
    [Research Fellow of the Royal  Swedish Academy of Sciences]
Dept. of Cell & Molecular Biology  University of Uppsala
                Biomedical Centre  Box 596
                SE-751 24 Uppsala  SWEDEN

    http://xray.bmc.uu.se/gerard/  mailto:gerard@xray.bmc.uu.se
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