In the discussion about temperature factor restraints
G. Kleywegt wrote:
>> * B-factor restraints test @ 960604
> ***********************************
>> * compare default B restraints in X-PLOR with Dale's restraints
> as posted on the xplor newsgroup
> (NOTE: this post does not quite implement Dale's method:
> - XPLOR would need something like: bsigma=(selection)=(selection)=target
> as it is now, every atom gets the target of the last bsigma
> statement it fits; for example:
> bsigma = ( name N or name CA ) = 4.6
> bsigma = ( name CA or name C ) = 7.4
> -> CA will get a target of 7.4 anyway
> - Dale's set has *directionality*)
> (NOTE: critique on Dale's paper: he never used Rfree to show that you
> actually get better models at any resolution !)
>> * first try with CRABPII holo, 1.8 A data, use near-final model
> still with Rfree (i.e., prior to final refinement against all data)
> do the following for several resolutions:
> - set all bs to 15 + Gaussian term as per normal xplor
> - refine with default xplor restraints
> - set bs to 15 + gaussian again
> - refine with pseudo-Dale restraints
>> Resol R/Rfree start Normal Bs Dale's Bs
> 2.0 0.270/0.287 0.202/0.226 0.193/0.220
> 2.2 0.259/0.275 0.197/0.220 0.185/0.216
> 2.4 0.250/0.267 0.191/0.218 0.178/0.212
> 2.6 0.242/0.263 0.184/0.219 0.169/0.214
> 3.0 0.230/0.252 0.175/0.211 0.161/0.205
>> -> in all cases pseudo-Dale is ~0.5 % better in Rfree
> however, also R is lower, but usually 2-3 times as much as Rfree
> -> pseudo-Dale seems to be slightly more accurate, but
> it also increases the extent of over-fitting (since R drops
> quite a bit more than Rfree)
>> * try the same with CBH2 native data (1.8 A):
>> Resol R/Rfree start Normal Bs Dale's Bs
> 2.0 0.232/0.247 0.169/0.198 0.159/0.197
> 2.4 0.215/0.232 0.156/0.193 0.143/0.191
> 3.0 0.196/0.210 0.140/0.182 0.123/0.179
>> -> same picture: 0.1-0.3% drop in Rfree at the expense of
> a drop in R which is 5-10 * larger
>> * -> stick to the old restraints in X-PLOR
>>> --------------------------------------------------------
> Gerard CD Kleywegt
> Presently at Yale (mailto:gkleyweg at laplace.csb.yale.edu)
> Normally in Uppsala (mailto:gerard at xray.bmc.uu.se)
>
I basically agree that there is a possibility of overfitting
with the 'pseudo-Dale' restraints. But there also seems to
be some information in them. So why stick to the old ones
if we can do better.
I propose a better implementation of the idea, rather than
just stick to whatever we did before.
But then, who's got the time?
Manfred Weiss
--
Manfred S. Weiss, Dr.
Institute of Molecular Biotechnology
Department of Structural Biology and Crystallography
Beutenbergstrasse 11
Postfach 100813 Phone: +49-3641-65-6070
D-07708 Jena Fax: +49-3641-65-6062
GERMANY Email: msweiss at imb-jena.de
