The default restraint weights in CNS are supposed to be changed depending upon the refinement details. The large radius of convergence of SA in CNS makes it very useful in the early stages of refinement. The optimize_wa.inp script is a semi-automatic method of doing this. Based upon the comments in the Eng and Huber paper I added the ability to automatically adjust the xray weights to produce a specified stereochemical bond rmsd to the PMB refinement program pmb_refine (-s flag). This program automates the refinement, in CNS, using different protocols depending on the flags given, and continues refinement until convergence is reached. In addition output files for CNS and COOT/CCP4MG can be generated easily.
Dirk's idea of increasing the x-ray term for a few rounds, to get out of local minima, is interesting, and would be easy to do in PMB. Along the same lines, if you have NCS, releasing NCS restraints for a round can help move the system out of a local minimum. I found this so useful that I added this ability to the pmb_refine program as an "NCS shake" (-n flag) option. Try it, it can really lower Rfree, even when you think that refinement has converged. I have also implemented Ian Tickle's variable sigma-B weighting of B-factor restraints (requires recompile of CNS). These additions to CNS all tend to reduce Rfree at any resolution.
PMB (for refinement using CNS 1.1) is available at
http://xray.utmb.edu/PMB/
Mark
On Wed, 2005-12-07 at 16:06 +0100, George M. Sheldrick wrote:
*** For details on how to be removed from this list visit the *** *** CCP4 home page http://www.ccp4.ac.uk *** Dirk, The way the relative retraint and X-ray weights are set (automatically) in SHELXL has the same affect as the scheme you describe, i.e. the model is restrained more tightly at the beginning of the refinement and more weakly as the agreement with the X-ray data improves. In addition there is a command (STIR) to gradually increase the resolution as the refinement progresses. The idea of relaxing the restraints and then tightening them again might indeed be a good way of getting out of local minima; see R. Stenkamp, Acta D61 (2005) 1599-1602 for a recent example in which this enabled a trans proline to switch to the (correct) cis peptide automatically. George Dirk Kostrewa wrote: > *** For details on how to be removed from this list visit the *** > *** CCP4 home page http://www.ccp4.ac.uk *** > > > Eleanor Dodson wrote: > >> All this is prob. true, but I repeat - >> should tight default stereochemistry be a requirement at the early >> stages of refinement at reso > 2.5A anyay? >> >> Eleanor >> > Good question - I usually tell our PhD students to have tight geometry > (rmsd bonds between 0.012-0.015 A) at the end of the refinement run, > hoping that this reduces overfitting and model bias by at least some > extend. But your question reminds me of a different refinement protocol, > recommended in an older TNT manual: first, refine with high weights on > the X-ray term to allow larger shifts with poor stereochemistry, then do > more refinement with lower weights on the X-ray term to tighten the > geometry, again. This scheme is probably almost forgotten, but should > still be useful! A complementary approach would be to start refinement > with high weights on the X-ray term AND lower maximum resolution to > allow a larger radius of convergence, and then include higher resolution > data and tighten your geometry. This is quite labour-intensive. If I > remember correctly, BUSTER/TNT does a smooth effective resolution > limitation dependent on the quality of the fit of the model to the data > by including several sources of variances in a Luzzati-type of scaling. > As the model improves during refinement and the total variance > decreases, the effective resolution apporaches the resolution limit of > the observed data. I think, this is very elegant and should be an option > in every modern refinement package. > > Best regards, > > Dirk. >
-- Best Regards, Mark -_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_ Mark A. White, Ph.D. Tel: Assistant Professor, Sealy Center for (409) 747-4747 Structural Biology and Molecular Biophysics Fax: Basic Science Building, Room 660C (409) 747-4745 University of Texas Medical Branch email: Galveston, TX 77555-0647 mailto://[EMAIL PROTECTED] http://xray.utmb.edu http://xray.utmb.edu/~white -_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_ |
