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Re: [ccp4bb] question about getting rid of model bias in refinement |
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CCP4bb navigationCCP4bb <-- 1999 <-- November 1999 <-- 30 November 1999Subject: Re: question about getting rid of model bias in refinement From: Anastassis Perrakis a {- dot -} perrakis {- at -} NKI {- dot -} NL Date: 2008-07-29 If resolution is around 2.0 or better, ARP/wARP is particularly powerful for such cases when model bias needs to be reduced. For more info: http://www.ncbi.nlm.nih.gov/pubmed/18094467?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum http://www.ncbi.nlm.nih.gov/pubmed/11567158?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Tassos On Jul 28, 2008, at 3:19, Sun Tang wrote: > > Hello Charlie, > > > Thank you very much for your comments. I mostly agree with you. > However, as far as I know most of the complexes structures are > solved with MR with the their apo-enzyme as search model and refined > the structures with CCP4 or CNS. I tried the simulated annealing > omitting the residue and 4 neighboring residues on each side and I > found the conformation are essentially the same. I also tried to use > composite omit-map calculation in CSN but I gave it because it took > several days of computer time but only finished only 1/4 of the > calculation. > > > I understand the starting from the beginning is one choice. I wonder > whether there are other easier ways in CCP4 to deal with this > situation because this problem is quite common in refinement. > > > I appreciate all the replies to my questions and I say "Thank you > very much" here. > > > Best, > > > Sun > > > --- On Sat, 7/26/08, Charles W. Carter Jr. > > From: Charles W. Carter Jr. > Subject: Re: [ccp4bb] question about getting rid of model bias in > refinement > To: CCP4BB@JISCMAIL.AC.UK > Date: Saturday, July 26, 2008, 3:15 PM > > Sun, > > I'm most of the way to one side of this debate: I believe that it > is not possible to emerge fully from model bias without avoiding it > in the first place with experimental phases. I may be overly > pessimistic, but have considerable experience supporting at least > skepticism. > > My interpretation of the experimental result you describe is that > the covariances among the parts of the structure you left in place > and those side chains you omitted is so strong and extensive that > you'll never see the correct density coming back upon refinement, > because other parts of the structure are ever so slightly off their > true mean positions to compensate for the (evidently false) > positions of the residues you omitted. Bill's suggestion that you > actually refine the structure using simulated annealing without the > omitted residues is an improvement over what you did, but it will > require many cycles to get a much better approximation, and there is > really no way to be sure when you can be confident. Starting the > entire refinement over is a more aggressive strategy. If you decide > to try this, you should examine the projection of the residue by > residue real-space correlation coefficients across the entire > sequence to ensure that you have only one population of values and > delete all residues that comprise any population that has a > distinctly different real-space correlation coefficient, building > them back into the structure as it refines. That is, you should > ensure that you don't begin refining any residues at the very > beginning for which there is evidence that they might be different > from their positions in your molecular replacement model. > > Charlie > > On Jul 26, 2008, at 2:12 PM, William G. Scott wrote: > >> Hi Sun: >> >> It might be worth doing a simulated annealing omit refinement in >> phenix or CNS, with the residues in question omitted. CNS also >> allows you to make a composite-omit map. I haven't seen that in >> phenix yet but presumably it is doable. >> >> Bill >> >> >> William G. Scott >> >> Contact info: >> http://chemistry.ucsc.edu/~wgscott/ >> >> >> On Jul 25, 2008, at 10:53 PM, Sun Tang wrote: >> >>> Hello Everyone, >>> >>> I have a question about getting rid of model bias in refinement >>> with refmac. I solved the structure with molecular replacement. >>> After final refinement of the structure, I found out some key >>> amino acids in the structure and wanted to make sure their >>> conformations are correct. I omitted these amino acids (by setting >>> occupancy to zero) and refined the structure. I manually fit the >>> amino acids into the density and refined the structure again. I >>> found these amino acids return to the precious conformations even >>> though the conformations I fit were different. Should I omit these >>> amino acids from the beginning of the refinement? What is the best >>> way to get rid of the model bias? Your suggestions are greatly >>> appreciated! >>> >>> Best, >>> >>> Sun >>> >>> >>> > > **********UNCrystallographers NOTE new website url****************** > carter@med.unc.edu > http://xtal.med.unc.edu/CARTER/Welcome.html > Department of Biochemistry and Biophysics CB 7260 > UNC Chapel Hill, Chapel Hill, NC 27599-7260 > Tel: 919 966-3263 > FAX 919 966-2852 > > > CCP4bb navigationCCP4bb <-- 1999 <-- November 1999 <-- 30 November 1999 |
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