[ccp4bb] Postdoctoral position in Toulouse, France
An eighteen-month postdoctoral position, funded by the French National Research Agency (ANR) is available immediately in the group of Lionel Mourey at the Institut de Pharmacologie et Biologie Structurale in Toulouse (http://www.ipbs.fr/english/). We are seeking a motivated scientist to join a research project on the structural and functional studies of an ensemble of polyketide synthases from M. tuberculosis and M. marinum, identified as promising targets for the development of new antimicrobial drugs against mycobacteria. You will have the opportunity to interact with two renowned teams from the Department of « Molecular Mechanisms of Mycobacterial Infections ». Experiments will involve a broad range of techniques including molecular biology, protein expression and purification, various methods of structure determination (X-ray crystallography, SAXS). Successful candidates should have a background in biochemistry and biophysics. Experience in molecular biology is a plus. Further informations may be obtained from Dr. Jean-Denis Pédelacq (telephone: +33-5-61-17-54-11; e-mail: jean-denis.pedel...@ipbs.fr). Closing date for applications is late january 2011. Written applications including a curriculum vitae and contact details for three referees should be forwarded to Jean-Denis Pédelacq, Structural Biophysics Group, IPBS-CNRS, 31077 Toulouse Cedex, France.
Re: [ccp4bb] diverging Rcryst and Rfree
Dear Ian, On Tue, Oct 26, 2010 at 05:15:50PM +0100, Ian Tickle wrote: Yes! - the critical piece of information that we're missing is the proportion of *all* structures that come from SG centres. Only knowing that can we do any serious statistics ... The point I was trying to make was not to blame SG centres (or comparing them with other groups) - I was concerned about technology mainly. Clearly, there was some problem at the point of deposition. I would have thought that especially in structures coming from SG centres there would be technology in place on both sides (at the SG centre and at the PDB site) to catch unusual values like an overall Rmerge of 0.99? Cheers Clemens PS: according to some simple search out of those 3026 entries 1473 are from SG centres and 1553 not. -- Ian On Tue, Oct 26, 2010 at 5:07 PM, Frank von Delft frank.vonde...@sgc.ox.ac.uk wrote: b) very large Rmerge values: Rmerge Rwork Rfree Rfree-Rwork Resolution - 0.9990 0.1815 0.2086 0.0271 1.80 SG center, unpublished 0.8700 0.1708 0.2270 0.0562 1.96 unpublished 0.7700 0.1870 0.2297 0.0428 1.56 0.7600 0.2380 0.2680 0.0300 2.50 SG center, unpublished 0.7000 0.1700 0.2253 0.0553 1.71 0.6400 0.2179 0.2715 0.0536 2.75 SG center, unpublished The most disturbing to me is that of those with very large overall Rmerge values, 3 come from structural genomics centers. Is that less or more disturbing than that the other 50% come from not-SG centers? Of course, the authors themselves may be willing to help correct the obvious typos -- which will presumably disappear forever once we can finally upload log files upon deposition (coming soon, I'm told). On an unrelated note, it's reassuring to see sound statistical principles -- averages, large N, avoidance of small number-anecdotes, and such rot -- continue not to be abandoned in the politics of science funding, he said airily. phx -- *** * Clemens Vonrhein, Ph.D. vonrhein AT GlobalPhasing DOT com * * Global Phasing Ltd. * Sheraton House, Castle Park * Cambridge CB3 0AX, UK *-- * BUSTER Development Group (http://www.globalphasing.com) ***
Re: [ccp4bb] Hardware question
I've been told by my (frighteningly geek-competent) colleague that the platters are identical, but the cheaper ones are those at the bottom of the Quality Control pile, which are therefore spun more slowly, and don't get any claims of reliability. (Have you checked the disk rotation speed? I imagine the Dell ones go much faster.) phx On 27/10/2010 02:52, Edward A. Berry wrote: Another question about computer hardware- If I configure a computer at the Dell site, it costs about $700 to add a 2TB SATA drive. On amazon.com or Staples or such, a 2TB drive costs ~$110. to $200 depending on brand. Are the Dell-installed drives much faster, or more reliable, or have a better warranty? After all, RAID is supposed to stand for redundant array of inexpensive disks, and we could afford a lot more redundancy at the Amazon.com price. And, are there any brands or models that should be avoided due to known reliability issues? Thanks, eab
Re: [ccp4bb] Against Method (R)
Yes, but what I think Frank is trying to point out is that the difference between Fobs and Fcalc in any given PDB entry is generally about 4-5 times larger than sigma(Fobs). In such situations, pretty much any standard statistical test will tell you that the model is highly unlikely to be correct. But that's not the question we are normally asking. It is highly unlikely that any model in biology is correct, if by correct you mean cannot be improved. Normally we ask the more modest question have I improved my model today over what it was yesterday?. I am not saying that everything in the PDB is wrong, just that the dominant source of error is a shortcoming of the models we use. Whatever this source of error is, it vastly overpowers the measurement error. That is, errors do not add linearly, but rather as squares, and 20%^2+5%^2 ~ 20%^2 . So, since the experimental error is only a minor contribution to the total error, it is arguably inappropriate to use it as a weight for each hkl. I think your logic has run off the track. The experimental error is an appropriate weight for the Fobs(hkl) because that is indeed the error for that observation. This is true independent of errors in the model. If you improve the model, that does not magically change the accuracy of the data. Sorry, still missing something: In the weighted Rfactor, we're weighting by the 1/sig**2 (right?) And the reason for that is, presumably, that when we add a term (Fo-Fc) but the Fo is crap (huge sigma), we need to ensure we don't add very much of it -- so we divide the term by the huge sigma. But what if Fc also is crap? Which it patently is: it's not even within 20% of Fo, never mind vaguely within sig(Fo). Why should we not be down-weighting those terms as well? Or can we ignore that because, since all terms are crap, we'd simply be down-weighting the entire Rw by a lot, and we'd be doing it for the Rw of both models we're comparing, so they'd cancel out when we take the ratio Rw1/Rw2? But if we're so happy to fudge away the huge gorilla in the room, why would we need to be religious about the little gnats on the floor (the sig(Fo))? Is there then really a difference between R1/R2 and Rw1/Rw2, for all practical purposes? (Of course, this is all for the ongoing case we don't know how to model the R-factor gap. And no, I haven't played with actual numbers...) phx.
Re: [ccp4bb] diverging Rcryst and Rfree [SEC=UNCLASSIFIED]
Anthony, I have used the minimum of -LLfree (i.e. same as maximum free likelihood) as a stopping rule for both weight optimisation and adding waters, the former because it seems to be well justified by theory (Gerard Bricogne's that is); also it's obviously very similar to Axel Brunger's min(Rfree) rule for weight optimisation which seems to work well. I use it for adding waters because it seems to give a reasonable number of waters. Changes in Rfree seem to roughly mirror changes in -LLfree, though they don't necessarily have minima at the same points in parameter space; I guess that's not surprising since unlike LLfree, Rfree is unweighted. Using the min(-LLfree) rule routinely for weight optimisation would be quite time consuming, so now I just use a target RMS-Z(bonds) value based on a linear fit of RMS-Z(bonds) vs resolution obtained from PDB-REDO refinements, where the min(-LLfree) rule was used. I haven't done a systematic study to see whether it can be used to decide whether or not adding TLS parameters improves the model, but in most of the cases I looked at (though admittedly not all) using TLS reduces Rfree and -LLfree, or at least doesn't cause them to increase significantly, so now I just use TLS routinely (like most other people I guess!). If I were being totally consistent with the use of my rule, I should really test -LLfree after using TLS and if it does increase then throw away the TLS model! This area could benefit from more careful investigation! I also tried min(Rfree-Rwork) as a stopping rule for weight optimisation and adding waters but it didn't give good results (i.e. the number of waters added seemed unrealistic). I haven't tried your rule min(Rfree-Rwork/2) in either case, and it may indeed turn out that it works better than mine. I was just interested to know whether you had arrived at your rule by experimentation, and if so how it compared with other possible rules. I do have one reservation about your rule; the same also applies to the min(Rfree-Rwork) rule: you can get situations where a decrease in both Rwork and Rfree corresponds to a worse model according to the rule, and conversely an increase in Rwork and Rfree corresponds to an improved model. This looks counter-intuitive to me: intuition tells me that a model which is more consistent with all of the experimental data (i.e. both the working and test sets) is a better model and one which is less consistent is a worse one. Admittedly intuition has been known to lead one astray and it may be the case that the model with lower Rwork Rfree is worse if judged by the deviations from the target geometry; however it doesn't seem likely that one would in practice get a lower Rfree with worse geometry unless really unlucky! For example, starting with a model with Rwork = 20, Rfree = 30 as before (test value = 20), consider a model with Rwork = 16, Rfree = 29: the test value = 21, so a worse model by your rule. Conversely consider a model with Rwork = 24, Rfree = 31: test value = 19, so a better model by your rule. As I said this behaviour is not peculiar to your rule; any rule which involves combining Rwork Rfree is likely to exhibit the same behaviour. Cheers -- Ian On Tue, Oct 26, 2010 at 2:52 PM, Ian Tickle ianj...@gmail.com wrote: Anthony, Your rule actually works on the difference (Rfree - Rwork/2), not (Rfree - Rwork) as you said, so is rather different from what most people seem to be using. For example let's say the current values are Rwork = 20, Rfree = 30, so your current test value is (30 - 20/2) = 20. Then according to your rule Rwork = 18, Rfree = 29 is equally acceptable (29 - 18/2 = 20, i.e. same test value), whereas Rwork = 16, Rfree = 29 would not be acceptable by your rule (29 - 16/2 = 21, so the test value is higher). Rwork = 18, Rfree = 28 would represent an improvement by your rule (28 - 18/2 = 19, i.e. a lower test value). You say this criterion provides a defined end-point, i.e. a minimum in the test value above. However wouldn't other linear combinations of Rwork Rfree also have a defined minimum value? In particular Rfree itself always has a defined minimum with respect to adding parameters or changing the weights, so would also satisfy your criterion. There has to be some additional criterion that you are relying on to select the particular linear combination (Rfree - Rwork.2) over any of the other possible ones? Cheers -- Ian On Tue, Oct 26, 2010 at 6:33 AM, DUFF, Anthony a...@ansto.gov.au wrote: One “rule of thumb” based on R and R-free divergence that I impress onto crystallography students is this: If a change in refinement strategy or parameters (eg loosening restraints, introducing TLS) or a round of addition of unimportant water molecules results in a reduction of R that is more than double the reduction in R-free, then don’t do it. This rule of thumb has proven successful in providing a defined end point for building and
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
Regarding the riding hydrogens: They are obviously not visible, but your protein in solution is also not visible but still has those weird riding hydrogens:-) Use them, they are there. And ther was a recent compendium of neutron scattering in one of our favorite journals if you really want to see them. Another rule to add: You are 98% done with refinement of your structure, does it really matter - I mean from a functional/ biological perspective ? Is it wrong to stop at some point ? This of course implies you've already passed rule 3-5 from Robbie. Just some Espresso-thoughts in the morning Jürgen .. Jürgen Bosch Johns Hopkins Bloomberg School of Public Health Department of Biochemistry Molecular Biology Johns Hopkins Malaria Research Institute 615 North Wolfe Street, W8708 Baltimore, MD 21205 Phone: +1-410-614-4742 Lab: +1-410-614-4894 Fax: +1-410-955-3655 http://web.mac.com/bosch_lab/ On Oct 27, 2010, at 1:29, Robbie Joosten robbie_joos...@hotmail.com wrote: Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all. Rule 1: If Rwork 20%, you are done. Rule 2: If R-free - Rwork 5%, your structure is wrong. Rule 3: At resolution X, the bond length rmsd should be than Y (What is the rmsd thing people keep talking about?) Rule 4: If your resolution is lower than X, you should not use_anisotropic_Bs/riding_hydrogens Rule 5: You should not build waters/alternates at resolutions lower than X Rule 6: You should do the final refinement with ALL reflections Rule 7: No one cares about getting the carbohydrates right Obviously, this list is not complete. I may also have overstated some of the rules to get the discussion going. Any addidtions are welcome. Cheers, Robbie Joosten Netherlands Cancer Institute Apologies if I have missed a recent relevant thread, but are lists of rules of thumb for model building and refinement? Anthony Anthony Duff Telephone: 02 9717 3493 Mob: 043 189 1076
Re: [ccp4bb] Help with Optimizing Crystals
Matt- You might want to try heating your protein to get rid of unfolded/improperly folded protein. We have used 37C for 10 min with good success, but a time course at different temperatures is the best way to determine which parameters are optimum for your protein. Heat-chill it on ice-centrifuge-- then set up your crystallization trays. It's a pretty quick test to see if this will work for your protein. Do you have any ligands for your protein? These have often been the key to getting good crystals in our lab. If you do have good ligands, you may want to express and/or purify your protein in the presence of these compounds. Good Luck! annie From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Jürgen Bosch Sent: Tuesday, October 26, 2010 5:46 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Help with Optimizing Crystals Hi. Here is some additional information. 1. The purification method that I used included Ni, tag cleavage, and SEC as a final step. I have tried samples from three different purification batches that range in purity, and even the batch with the worst purity seems to produce crystals. Resource Q ? two or more species perhaps ? Does it run as a monomer dimer multimer on your SEC ? 2. The protein is a proteolyzed fragment since the full length version did not crystallize. Mutagenesis and methylation, however, may be techniques to consider since the protein contains quite a few lysines. 3. There are not any detergents in the buffer, so these are not detergent crystals. The protein buffer just contains Tris at pH 8, NaCl, and DTT. 4. Some experiments that I have done thus far seem to suggest that the crystals are protein. Izit dye soaks well into the crystals, and the few crystals that I shot previously did not produce any diffraction pattern whatsoever. However, I have had difficulty seeming them on a gel and they are a bit tough to break. Do they float or do they sink quickly when you try to mount them ? 5. I tried seeding previously as follows: I broke some crystals, made a seed stock, dipped in a hair, and did serial streak seeding. After seeding, I usually saw small disks or clusters along the path of the hair but nothing larger or better looking. I also had one more question. Has anyone had an instance where changing the precipitation condition or including an additive improved diffraction but did not drastically change the shape of the protein? If so, I may just try further optimization with the current conditions and shoot some more crystals. The additive screen from Hampton is not bad and can make a big difference. A different topic is it a direct cryo what you are using as a condition ? If not what do you use a s a cryo ? Have you tried the old-fashioned way of shooting at crystals at room temperature using capillaries (WTHIT ?) You might be killing your crystal by trying to cryo it is what I'm trying to say here. Jürgen Thanks for all the helpful advice thus far, Matt
Re: [ccp4bb] Against Method (R)
On Tue, 2010-10-26 at 21:16 +0100, Frank von Delft wrote: the errors in our measurements apparently have no bearing whatsoever on the errors in our models This would mean there is no point trying to get better crystals, right? Or am I also wrong to assume that the dataset with higher I/sigma in the highest resolution shell will give me a better model? On a related point - why is Rmerge considered to be the limiting value for the R? Isn't Rmerge a poorly defined measure itself that deteriorates at least in some circumstances (e.g. increased redundancy)? Specifically, shouldn't ideal R approximate 0.5*sigmaI/I? Cheers, Ed. -- I'd jump in myself, if I weren't so good at whistling. Julian, King of Lemurs
Re: [ccp4bb] Against Method (R)
On Wed, 27 Oct 2010, Frank von Delft wrote: So, since the experimental error is only a minor contribution to the total error, it is arguably inappropriate to use it as a weight for each hkl. I think your logic has run off the track. The experimental error is an appropriate weight for the Fobs(hkl) because that is indeed the error for that observation. This is true independent of errors in the model. If you improve the model, that does not magically change the accuracy of the data. Sorry, still missing something: In the weighted Rfactor, we're weighting by the 1/sig**2 (right?) And the reason for that is, presumably, that when we add a term (Fo-Fc) but the Fo is crap (huge sigma), we need to ensure we don't add very much of it -- so we divide the term by the huge sigma. Correct. But what if Fc also is crap? Which it patently is: it's not even within 20% of Fo, never mind vaguely within sig(Fo). Why should we not be down-weighting those terms as well? Because here we want the exact opposite. If Fc is hugely different from a well-measured Fobs then it is a sensitive indicator of a problem with the model. Why would we want to down-weight it? Consider the extreme case: if you down-weight all reflections for which Fc does not already agree with Fo, then you will always conclude that the current model, no matter what random drawer you pulled it from, is in fine shape. Or can we ignore that because, since all terms are crap, we'd simply be down-weighting the entire Rw by a lot, and we'd be doing it for the Rw of both models we're comparing, so they'd cancel out when we take the ratio Rw1/Rw2? Not sure I follow this. But if we're so happy to fudge away the huge gorilla in the room, why would we need to be religious about the little gnats on the floor (the sig(Fo))? Is there then really a difference between R1/R2 and Rw1/Rw2, for all practical purposes? Yes. That was the message of the 1970 Ford Rollet paper that Ian provided a link for. Ethan (Of course, this is all for the ongoing case we don't know how to model the R-factor gap. And no, I haven't played with actual numbers...) phx.
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you have to apply more sophisticated test such as Ethan pointed out (HR tests) or Ian uses (LL-tests). And once you know how to do that, you do not need any rules of thumb anyhow. So I opt for a formal burial of these rules of thumb and a toast to evidence and plausibility. And, as Gerard B said in other words so nicely: Si tacuisses, philosophus mansisses. BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Robbie Joosten Sent: Tuesday, October 26, 2010 10:29 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all. Rule 1: If Rwork 20%, you are done. Rule 2: If R-free - Rwork 5%, your structure is wrong. Rule 3: At resolution X, the bond length rmsd should be than Y (What is the rmsd thing people keep talking about?) Rule 4: If your resolution is lower than X, you should not use_anisotropic_Bs/riding_hydrogens Rule 5: You should not build waters/alternates at resolutions lower than X Rule 6: You should do the final refinement with ALL reflections Rule 7: No one cares about getting the carbohydrates right Obviously, this list is not complete. I may also have overstated some of the rules to get the discussion going. Any addidtions are welcome. Cheers, Robbie Joosten Netherlands Cancer Institute Apologies if I have missed a recent relevant thread, but are lists of rules of thumb for model building and refinement? Anthony Anthony Duff Telephone: 02 9717 3493 Mob: 043 189 1076 =
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
Surely the best model is the one that the referees for your paper are happy with? I have found referees to impose seemingly random and arbitrary standards that sometime require a lot of effort to comply with but result in little to no impact on the biology being described. Mind you discussions on this email list can be a useful resource for telling referee's why you don't think you should comply with their rule of thumb. Simon On 27 Oct 2010, at 20:11, Bernhard Rupp (Hofkristallrat a.D.) wrote: Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you have to apply more sophisticated test such as Ethan pointed out (HR tests) or Ian uses (LL-tests). And once you know how to do that, you do not need any rules of thumb anyhow. So I opt for a formal burial of these rules of thumb and a toast to evidence and plausibility. And, as Gerard B said in other words so nicely: Si tacuisses, philosophus mansisses. BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Robbie Joosten Sent: Tuesday, October 26, 2010 10:29 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all. Rule 1: If Rwork 20%, you are done. Rule 2: If R-free - Rwork 5%, your structure is wrong. Rule 3: At resolution X, the bond length rmsd should be than Y (What is the rmsd thing people keep talking about?) Rule 4: If your resolution is lower than X, you should not use_anisotropic_Bs/riding_hydrogens Rule 5: You should not build waters/alternates at resolutions lower than X Rule 6: You should do the final refinement with ALL reflections Rule 7: No one cares about getting the carbohydrates right Obviously, this list is not complete. I may also have overstated some of the rules to get the discussion going. Any addidtions are welcome. Cheers, Robbie Joosten Netherlands Cancer Institute Apologies if I have missed a recent relevant thread, but are lists of rules of thumb for model building and refinement? Anthony Anthony Duff Telephone: 02 9717 3493 Mob: 043 189 1076 =
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
perhaps we should campaign for it to be obligatory to provide the pdb and structure factor file to the journal, and thus referees, upon submission? Then he can look for himself to see that building and refinement have been performed satisfactorily. Mark Surely the best model is the one that the referees for your paper are happy with? I have found referees to impose seemingly random and arbitrary standards that sometime require a lot of effort to comply with but result in little to no impact on the biology being described. Mind you discussions on this email list can be a useful resource for telling referee's why you don't think you should comply with their rule of thumb. Simon On 27 Oct 2010, at 20:11, Bernhard Rupp (Hofkristallrat a.D.) wrote: Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you have to apply more sophisticated test such as Ethan pointed out (HR tests) or Ian uses (LL-tests). And once you know how to do that, you do not need any rules of thumb anyhow. So I opt for a formal burial of these rules of thumb and a toast to evidence and plausibility. And, as Gerard B said in other words so nicely: Si tacuisses, philosophus mansisses. BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Robbie Joosten Sent: Tuesday, October 26, 2010 10:29 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all. Rule 1: If Rwork 20%, you are done. Rule 2: If R-free - Rwork 5%, your structure is wrong. Rule 3: At resolution X, the bond length rmsd should be than Y (What is the rmsd thing people keep talking about?) Rule 4: If your resolution is lower than X, you should not use_anisotropic_Bs/riding_hydrogens Rule 5: You should not build waters/alternates at resolutions lower than X Rule 6: You should do the final refinement with ALL reflections Rule 7: No one cares about getting the carbohydrates right Obviously, this list is not complete. I may also have overstated some of the rules to get the discussion going. Any addidtions are welcome. Cheers, Robbie Joosten Netherlands Cancer Institute Apologies if I have missed a recent relevant thread, but are lists of rules of thumb for model building and refinement? Anthony Anthony Duff Telephone: 02 9717 3493 Mob: 043 189 1076 = Mark J van Raaij Laboratorio M-4 Dpto de Estructura de Macromoléculas Centro Nacional de Biotecnología - CSIC c/Darwin 3, Campus Cantoblanco 28049 Madrid tel. 91 585 4616 email: mjvanra...@cnb.csic.es
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
One can also release structure in the PDB prior to submission - I believe the HPUB option is rarely (if ever) justified. Ed. On Wed, 2010-10-27 at 22:56 +0200, VAN RAAIJ , MARK JOHAN wrote: perhaps we should campaign for it to be obligatory to provide the pdb and structure factor file to the journal, and thus referees, upon submission? Then he can look for himself to see that building and refinement have been performed satisfactorily. Mark Surely the best model is the one that the referees for your paper are happy with? I have found referees to impose seemingly random and arbitrary standards that sometime require a lot of effort to comply with but result in little to no impact on the biology being described. Mind you discussions on this email list can be a useful resource for telling referee's why you don't think you should comply with their rule of thumb. Simon On 27 Oct 2010, at 20:11, Bernhard Rupp (Hofkristallrat a.D.) wrote: Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you have to apply more sophisticated test such as Ethan pointed out (HR tests) or Ian uses (LL-tests). And once you know how to do that, you do not need any rules of thumb anyhow. So I opt for a formal burial of these rules of thumb and a toast to evidence and plausibility. And, as Gerard B said in other words so nicely: Si tacuisses, philosophus mansisses. BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Robbie Joosten Sent: Tuesday, October 26, 2010 10:29 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all. Rule 1: If Rwork 20%, you are done. Rule 2: If R-free - Rwork 5%, your structure is wrong. Rule 3: At resolution X, the bond length rmsd should be than Y (What is the rmsd thing people keep talking about?) Rule 4: If your resolution is lower than X, you should not use_anisotropic_Bs/riding_hydrogens Rule 5: You should not build waters/alternates at resolutions lower than X Rule 6: You should do the final refinement with ALL reflections Rule 7: No one cares about getting the carbohydrates right Obviously, this list is not complete. I may also have overstated some of the rules to get the discussion going. Any addidtions are welcome. Cheers, Robbie Joosten Netherlands Cancer Institute Apologies if I have missed a recent relevant thread, but are lists of rules of thumb for model building and refinement? Anthony Anthony Duff Telephone: 02 9717 3493 Mob: 043 189 1076 = Mark J van Raaij Laboratorio M-4 Dpto de Estructura de Macromoléculas Centro Nacional de Biotecnología - CSIC c/Darwin 3, Campus Cantoblanco 28049 Madrid tel. 91 585 4616 email: mjvanra...@cnb.csic.es -- I'd jump in myself, if I weren't so good at whistling. Julian, King of Lemurs
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
They do send both, if you explicitly ask as a referee and threaten otherwise not to review, but who a) has and takes the time to make a map and look at the parts relevant to discussion b) knows how to do that properly and with confidence (otherwise it’s worthless) A suggestion to Nature to always pair a crystallographic technical reviewer with no stake in the subject of study with those evaluating the biological or whatever thematic merits are, was not deemed worthy of response. It would admittedly require intimate knowledge of the field and quite some work for the editor, that is for sure. BR From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of VAN RAAIJ , MARK JOHAN Sent: Wednesday, October 27, 2010 1:57 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) perhaps we should campaign for it to be obligatory to provide the pdb and structure factor file to the journal, and thus referees, upon submission? Then he can look for himself to see that building and refinement have been performed satisfactorily. Mark Surely the best model is the one that the referees for your paper are happy with? I have found referees to impose seemingly random and arbitrary standards that sometime require a lot of effort to comply with but result in little to no impact on the biology being described. Mind you discussions on this email list can be a useful resource for telling referee's why you don't think you should comply with their rule of thumb. Simon On 27 Oct 2010, at 20:11, Bernhard Rupp (Hofkristallrat a.D.) wrote: Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you have to apply more sophisticated test such as Ethan pointed out (HR tests) or Ian uses (LL-tests). And once you know how to do that, you do not need any rules of thumb anyhow. So I opt for a formal burial of these rules of thumb and a toast to evidence and plausibility. And, as Gerard B said in other words so nicely: Si tacuisses, philosophus mansisses. BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Robbie Joosten Sent: Tuesday, October 26, 2010 10:29 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all. Rule 1: If Rwork 20%, you are done. Rule 2: If R-free - Rwork 5%, your structure is wrong. Rule 3: At resolution X, the bond length rmsd should be than Y (What is the rmsd thing people keep talking about?) Rule 4: If your resolution is lower than X, you should not use_anisotropic_Bs/riding_hydrogens Rule 5: You should not build waters/alternates at resolutions lower than X Rule 6: You should do the final refinement with ALL reflections Rule 7: No one cares about getting the carbohydrates right Obviously, this list is not complete. I may also have overstated some of the rules to get the discussion going. Any addidtions are welcome. Cheers, Robbie Joosten Netherlands Cancer Institute Apologies if I have missed a recent relevant thread, but are lists of rules of thumb for model building and refinement? Anthony Anthony Duff Telephone: 02 9717 3493 Mob: 043 189 1076 = Mark J van Raaij Laboratorio M-4 Dpto de Estructura de Macromoléculas Centro Nacional de Biotecnología - CSIC c/Darwin 3, Campus Cantoblanco 28049 Madrid tel. 91 585 4616 email: mjvanra...@cnb.csic.es
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
On Wed, Oct 27, 2010 at 2:20 PM, Ed Pozharski epozh...@umaryland.eduwrote: One can also release structure in the PDB prior to submission - I believe the HPUB option is rarely (if ever) justified. What's to prevent your closest competitor from downloading the structure and using it to solve and refine his or her own data? Then all they need to do is call their buddies from grad school who are now senior journal editors, and weasel their way into a high-profile article with minimal review. Surely everyone who has spent time in academia knows at least one tenured professor who does this. In principle, I mostly agree with your argument, but you'd need to convince all journals to agree to an embargo period for released-but-unpublished PDB entries - and it would still be very difficult to enforce. The PDB's current rules aren't always optimal, but it's not even close to as big a mess as science publishing. -Nat
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
Ø What's to prevent your closest competitor from downloading the structure and using it to solve and refine his or her own data? Integrity perhaps? Ahh stupid me that is a verboten word. My original title of the recent JApplCryst commentary was a nice alliteration - Scientific inquiry, inference, and integrity in the biomolecular crystallography curriculum. As you see , integrity had to go to prevent liability issues. Its does not seem to be a liability to publish nonsense, though. Then all they need to do is call their buddies from grad school who are now senior journal editors, and weasel their way into a high-profile article with minimal review. Surely everyone who has spent time in academia knows at least one tenured professor who does this. In principle, I mostly agree with your argument, but you'd need to convince all journals to agree to an embargo period for released-but-unpublished PDB entries - and it would still be very difficult to enforce. The PDB's current rules aren't always optimal, but it's not even close to as big a mess as science publishing. Again, if every technically competent reviewer asks- if deemed necessary- for coordinates and declines review if they are refused, that might change. -Nat
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
Sorry I mean coordinates AND data of course. Again, if every technically competent reviewer asks- if deemed necessary- for coordinates and data and declines review if they are refused, that might change. -Nat
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
Surely the best model is the one that the referees for your paper are happy with? That may be the sad and pragmatic wisdom, but certainly not a truth we should accept... I have found referees to impose seemingly random and arbitrary standards a) Reviewers are people belonging to a certain population, characterized by say a property 'review quality' that follows a certain distribution. Irrespective of the actual shape of that parent distribution, the central limit theorem informs us that if you sample this distribution reasonably often, the sampling distribution will be normal. That means, that half of the reviews will be below average review quality, and half above. Unfortunately, the mean of that distribution is b) a function of journal editor quality (they pick the reviewers after all) and c) affected by systematic errors such as your reputation and the chance that you yourself might sit on a reviewer's grant review panel By combining a, b, c you can get a fairly good assessment of the joint probability of what report you will receive. You do notice that model quality is not a parameter in this model, because we can neglect marginal second order contributions. Mind you discussions on this email list can be a useful resource for telling referee's why you don't think you should comply with their rule of thumb. I agree and sympathize with your optimism, but I am afraid that those who might need this education are not the ones who seek it. I.e., reading the bb complicates matters (simplicity being one benefit of ROTs) and you can't build an empire wasting time on such things. Good luck with your reviews! BR Simon On 27 Oct 2010, at 20:11, Bernhard Rupp (Hofkristallrat a.D.) wrote: Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you have to apply more sophisticated test such as Ethan pointed out (HR tests) or Ian uses (LL-tests). And once you know how to do that, you do not need any rules of thumb anyhow. So I opt for a formal burial of these rules of thumb and a toast to evidence and plausibility. And, as Gerard B said in other words so nicely: Si tacuisses, philosophus mansisses. BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Robbie Joosten Sent: Tuesday, October 26, 2010 10:29 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all. Rule 1: If Rwork 20%, you are done. Rule 2: If R-free - Rwork 5%, your structure is wrong. Rule 3: At resolution X, the bond length rmsd should be than Y (What is the rmsd thing people keep talking about?) Rule 4: If your resolution is lower than X, you should not use_anisotropic_Bs/riding_hydrogens Rule 5: You should not build waters/alternates at resolutions lower than X Rule 6: You should do the final refinement with ALL reflections Rule 7: No one cares about getting the carbohydrates right Obviously, this list is not complete. I may also have overstated some of the rules to get the discussion going. Any addidtions are welcome. Cheers, Robbie Joosten Netherlands Cancer Institute Apologies if I have missed a recent relevant thread, but are lists of rules of thumb for model building and refinement? Anthony Anthony Duff Telephone: 02 9717 3493 Mob: 043 189 1076 =
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
Journal editors need to know when the reviewer they trusted is completely out to lunch. So please don't just silently knuckle under! It may make no difference for Nature, but my impression has been that rigorous journals like JMB do care about review quality. Phoebe = Phoebe A. Rice Dept. of Biochemistry Molecular Biology The University of Chicago phone 773 834 1723 http://bmb.bsd.uchicago.edu/Faculty_and_Research/01_Faculty/01_Faculty_Alphabetically.php?faculty_id=123 http://www.rsc.org/shop/books/2008/9780854042722.asp Original message Date: Wed, 27 Oct 2010 15:13:03 -0700 From: CCP4 bulletin board CCP4BB@JISCMAIL.AC.UK (on behalf of Bernhard Rupp (Hofkristallrat a.D.) hofkristall...@gmail.com) Subject: Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) To: CCP4BB@JISCMAIL.AC.UK Surely the best model is the one that the referees for your paper are happy with? That may be the sad and pragmatic wisdom, but certainly not a truth we should accept... I have found referees to impose seemingly random and arbitrary standards a) Reviewers are people belonging to a certain population, characterized by say a property 'review quality' that follows a certain distribution. Irrespective of the actual shape of that parent distribution, the central limit theorem informs us that if you sample this distribution reasonably often, the sampling distribution will be normal. That means, that half of the reviews will be below average review quality, and half above. Unfortunately, the mean of that distribution is b) a function of journal editor quality (they pick the reviewers after all) and c) affected by systematic errors such as your reputation and the chance that you yourself might sit on a reviewer's grant review panel By combining a, b, c you can get a fairly good assessment of the joint probability of what report you will receive. You do notice that model quality is not a parameter in this model, because we can neglect marginal second order contributions. Mind you discussions on this email list can be a useful resource for telling referee's why you don't think you should comply with their rule of thumb. I agree and sympathize with your optimism, but I am afraid that those who might need this education are not the ones who seek it. I.e., reading the bb complicates matters (simplicity being one benefit of ROTs) and you can't build an empire wasting time on such things. Good luck with your reviews! BR Simon On 27 Oct 2010, at 20:11, Bernhard Rupp (Hofkristallrat a.D.) wrote: Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you have to apply more sophisticated test such as Ethan pointed out (HR tests) or Ian uses (LL-tests). And once you know how to do that, you do not need any rules of thumb anyhow. So I opt for a formal burial of these rules of thumb and a toast to evidence and plausibility. And, as Gerard B said in other words so nicely: Si tacuisses, philosophus mansisses. BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Robbie Joosten Sent: Tuesday, October 26, 2010 10:29 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all. Rule 1: If Rwork 20%, you are done. Rule 2: If R-free - Rwork 5%, your structure is wrong. Rule 3: At resolution X, the bond length rmsd should be than Y (What is the rmsd thing people keep talking about?) Rule 4: If your resolution is lower than X, you should not
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
What about the possibility of double-blind review? I have actually wondered why the reviewers should be given the author info--does that determine the quality of the work? Am I missing some obvious reason why reviewers should know who the authors are? JPK On Wed, Oct 27, 2010 at 5:50 PM, Phoebe Rice pr...@uchicago.edu wrote: Journal editors need to know when the reviewer they trusted is completely out to lunch. So please don't just silently knuckle under! It may make no difference for Nature, but my impression has been that rigorous journals like JMB do care about review quality. Phoebe = Phoebe A. Rice Dept. of Biochemistry Molecular Biology The University of Chicago phone 773 834 1723 http://bmb.bsd.uchicago.edu/Faculty_and_Research/01_Faculty/01_Faculty_Alphabetically.php?faculty_id=123 http://www.rsc.org/shop/books/2008/9780854042722.asp Original message Date: Wed, 27 Oct 2010 15:13:03 -0700 From: CCP4 bulletin board CCP4BB@JISCMAIL.AC.UK (on behalf of Bernhard Rupp (Hofkristallrat a.D.) hofkristall...@gmail.com) Subject: Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) To: CCP4BB@JISCMAIL.AC.UK Surely the best model is the one that the referees for your paper are happy with? That may be the sad and pragmatic wisdom, but certainly not a truth we should accept... I have found referees to impose seemingly random and arbitrary standards a) Reviewers are people belonging to a certain population, characterized by say a property 'review quality' that follows a certain distribution. Irrespective of the actual shape of that parent distribution, the central limit theorem informs us that if you sample this distribution reasonably often, the sampling distribution will be normal. That means, that half of the reviews will be below average review quality, and half above. Unfortunately, the mean of that distribution is b) a function of journal editor quality (they pick the reviewers after all) and c) affected by systematic errors such as your reputation and the chance that you yourself might sit on a reviewer's grant review panel By combining a, b, c you can get a fairly good assessment of the joint probability of what report you will receive. You do notice that model quality is not a parameter in this model, because we can neglect marginal second order contributions. Mind you discussions on this email list can be a useful resource for telling referee's why you don't think you should comply with their rule of thumb. I agree and sympathize with your optimism, but I am afraid that those who might need this education are not the ones who seek it. I.e., reading the bb complicates matters (simplicity being one benefit of ROTs) and you can't build an empire wasting time on such things. Good luck with your reviews! BR Simon On 27 Oct 2010, at 20:11, Bernhard Rupp (Hofkristallrat a.D.) wrote: Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you have to apply more sophisticated test such as Ethan pointed out (HR tests) or Ian uses (LL-tests). And once you know how to do that, you do not need any rules of thumb anyhow. So I opt for a formal burial of these rules of thumb and a toast to evidence and plausibility. And, as Gerard B said in other words so nicely: Si tacuisses, philosophus mansisses. BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Robbie Joosten Sent: Tuesday, October 26, 2010 10:29 PM To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) Dear Anthony, That is an excellent question! I believe there are quite a lot of 'rules of thumb' going around. Some of them seem to lead to very dogmatic thinking and have caused (refereeing) trouble for good structures and lack of trouble for bad structures. A lot of them were discussed at the CCP4BB so it may be nice to try to list them all.
[ccp4bb] Bug in c_truncate?
Hello, I've been struggling with F2MTZ and importing my hkl file into mtz by 'keeping existing freeR data'. I keep getting the error Problem with FREE column in input file. All flags apparently identical. Check input file. At the end of the day, it appears that this only happens in ctruncate and not in the old_truncate instead of ctruncate. Has anyone experienced a similar problem? Peter
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
Why not double open review? If I have something reasonable to say, I should be able to sign it. Particularly if the publicly purported point of review is to make the manuscript better. And imagine what wonderful open hostility we would enjoy instead of all these hidden grudges! You would never have to preemptively condemn a paper on grounds of suspicion that it is from someone who might have reviewed you equally loathful earlier. You actually know that you are creaming the right bastard! A more serious question for the editors amongst us: Can I publish review comments or are they covered under some confidentiality rule? Some of these gems are quite worthy public entertainment. Best, BR -Original Message- From: CCP4 bulletin board [mailto:ccp...@jiscmail.ac.uk] On Behalf Of Jacob Keller Sent: Wednesday, October 27, 2010 6:02 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) What about the possibility of double-blind review? I have actually wondered why the reviewers should be given the author info--does that determine the quality of the work? Am I missing some obvious reason why reviewers should know who the authors are? JPK On Wed, Oct 27, 2010 at 5:50 PM, Phoebe Rice pr...@uchicago.edu wrote: Journal editors need to know when the reviewer they trusted is completely out to lunch. So please don't just silently knuckle under! It may make no difference for Nature, but my impression has been that rigorous journals like JMB do care about review quality. Phoebe = Phoebe A. Rice Dept. of Biochemistry Molecular Biology The University of Chicago phone 773 834 1723 http://bmb.bsd.uchicago.edu/Faculty_and_Research/01_Faculty/01_Faculty _Alphabetically.php?faculty_id=123 http://www.rsc.org/shop/books/2008/9780854042722.asp Original message Date: Wed, 27 Oct 2010 15:13:03 -0700 From: CCP4 bulletin board CCP4BB@JISCMAIL.AC.UK (on behalf of Bernhard Rupp (Hofkristallrat a.D.) hofkristall...@gmail.com) Subject: Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree) To: CCP4BB@JISCMAIL.AC.UK Surely the best model is the one that the referees for your paper are happy with? That may be the sad and pragmatic wisdom, but certainly not a truth we should accept... I have found referees to impose seemingly random and arbitrary standards a) Reviewers are people belonging to a certain population, characterized by say a property 'review quality' that follows a certain distribution. Irrespective of the actual shape of that parent distribution, the central limit theorem informs us that if you sample this distribution reasonably often, the sampling distribution will be normal. That means, that half of the reviews will be below average review quality, and half above. Unfortunately, the mean of that distribution is b) a function of journal editor quality (they pick the reviewers after all) and c) affected by systematic errors such as your reputation and the chance that you yourself might sit on a reviewer's grant review panel By combining a, b, c you can get a fairly good assessment of the joint probability of what report you will receive. You do notice that model quality is not a parameter in this model, because we can neglect marginal second order contributions. Mind you discussions on this email list can be a useful resource for telling referee's why you don't think you should comply with their rule of thumb. I agree and sympathize with your optimism, but I am afraid that those who might need this education are not the ones who seek it. I.e., reading the bb complicates matters (simplicity being one benefit of ROTs) and you can't build an empire wasting time on such things. Good luck with your reviews! BR Simon On 27 Oct 2010, at 20:11, Bernhard Rupp (Hofkristallrat a.D.) wrote: Dear Young and Impressionable readers: I second-guess here that Robbie's intent - after re-refining many many PDB structures, seeing dreadful things, and becoming a hardened cynic - is to provoke more discussion in order to put in perspective - if not debunk- almost all of these rules. So it may be better to pretend you have never heard of these rules. Your crystallographic life might be a happier and less biased one. If you follow this simple procedure (not a rule) The model that fits the primary evidence (minimally biased electron density) best and is at the same time physically meaningful, is the best model, i. e., all plausibly accountable electron density (and not more) is modeled. This process of course does require a little work (like looking through all of the model, not just the interesting parts, and thinking what makes sense) but may lead to additional and unexpected insights. And in almost all cases, you will get a model with plausible statistics, without any reliance on rules. For some decisions regarding global parameterizations you
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
What about the possibility of double-blind review? I have actually wondered why the reviewers should be given the author info--does that determine the quality of the work? Am I missing some obvious reason why reviewers should know who the authors are? I've always felt (and advocated long time ago on Usenet) that the current review system gets everything exactly backwards. 1) To prevent hatchet jobs of a review, reviewers should not be anonymous. 2) To prevent systematic bias by things completely irrelevant to the review job, reviewers (and handling editors!) should not be given authors' names and institutions. I think that the moment #1 happens, each review will start taking much, much longer time than it is now. This means that either a lot less would ever be reviewed and published or -oh horror- postdocs and graduate students would need to be reviewers, too. IMHO, both outcomes are perfectly acceptable. #2 is difficult in practice because self-references and all kind of hints can always be planted to make sure everyone knows the names. But maybe if such advertisements are frowed upon by the community, their incidence will be low enough to be a problem? -- Dima
Re: [ccp4bb] Rules of thumb (was diverging Rcryst and Rfree)
It's fun to watch my innocent little comment unfold into a pandemonium of email :) That's why i love this mailing list. Seriously though, there seems to be two salient things said by many people in many different ways: 1. it's a good idea to look at the model in detail, and pay attention to structure-based warnings rather than purely number-based ones. Pretty straightforward. 2. there is a huge gap between the reality of academic peer-review process and the (not so silent) desires of the crystallographic community. Not a surprise either. Thank goodness I am in industry. We get 'laid off' a lot (a well recognized occupational hazard) but at least we don't live die by our publication records. Artem
