Re: [ccp4bb] what is isomorphous?
Hi Carlos, In a practical setting you don't have to be very purist. The memory with respect to the reflection data is lost if you refine to convergence. Now there was are recent discussion on refinement convergence and again you can be quite purist here. However, if you go through a few cycles of rebuilding and refinement until R and R-free are stable, you are in clear with respect to cheating.* HTH, Robbie When working with ligands there a much more severe ways of cheating (oneself). > -Original Message- > From: CCP4 bulletin board On Behalf Of Carlos > Kikuti > Sent: Thursday, February 8, 2024 00:24 > To: CCP4BB@JISCMAIL.AC.UK > Subject: Re: [ccp4bb] what is isomorphous? > > Hello! > > I have to admit my maths is a bit lazy, but this discussion got me stitched > up, > because of a point I believe has not been addressed: the Rfree flags. I've > been > trained to import Rfree flags whenever the crystals have the same space group > and similar cell dimensions to the search model for molecular replacement - > this to avoid "cheating" the Rfree validation with reflections that the search > model has already 'seen'. We often work with series of crystals of the same > proteins with different ligands, which give groups of very similar unit > cells. So > far my strategy has been to mirror the Rfree flags (using the -ref or -rfree > keyword in Autoproc) whenever the biggest difference in one of the dimensions > is 5% - number just out of my instinct, taking in account the Rmerge of ~0.1 > or > less in the good cases. Maximum resolutions are between 2.7 and 1.9 > angstroms. Now considering the fact that isomorphism depends on resolution, > it makes me reconsider the 5% cut-off: this might be fine at the low > resolution, > but what about the higher resolution shells? What would be the best way to > proceed in these cases, then? Because the level of 'cheating' will also vary > with > resolution... > > Carlos > > On Sun, Dec 31, 2023 at 5:21 PM James Holton <mailto:jmhol...@lbl.gov> > wrote: > > > > Ahh yes. I still have the very helpful email I got from Dame Louise > Johnson in 2010. I don't think she would mind my quoting it here: > > > > Dear James > > I was sorry to miss you when you were at Diamond - I was in > Germany. > > The story of the two forms of lysozyme crystals goes back to > about 1964 when > it was found that the diffraction patterns from different > crystals > could be > placed in one of two classes depending on their intensities. > This discovery > was a big set back at the time and I can remember a lecture > title being > changed from the 'The structure of lysozyme' to 'The structure > of lysozyme > two steps forward and one step back'. Thereafter the crystals > were > screened based on intensities of the (11,11,l) rows to > distinguish them > (e.g. 11,11,4 > 11,11,5 in one form and vice versa in another). > Data were > collected only for those that fulfilled the Type II criteria. > (These > reflections were easy to measure on the linear diffractometer > because > crystals were mounted to rotate about the diagonal axis). As I > recall both > Type I and Type II could be found in the same crystallisation > batch . > Although sometimes the external morphology allowed > recognition this was not > infallible. > > The structure was based on Type II crystals. Later a graduate > student Helen > Handoll examined Type I. The work, which was in the early days > and before > refinement programmes, seemed to suggest that the > differences lay in the > arrangement of water or chloride molecules (Lysozyme was > crystallised from > NaCl). But the work was never written up. Keith Wilson at one > stage was > following this up as lysozyme was being used to test data > collection > strategies but I do not know the outcome. > > An account of this is given in International Table Volume F > (Rossmann and > Arnold edited 2001) p760. > > Tony North was much involved in sorting this out and if you > wanted more info > he would be the person to contact. > > I hope this is helpful. Do let me know if you need more. > > Best wishes > > Louise > > Armed with this advice, I searched the PDB using what I call the &g
Re: [ccp4bb] what is isomorphous?
> changes in Fobs due to the structural shift become larger than SIGFobs, > then you start having "non-isomorphism". For the common example of merging > data from multiple crystals, non-isomorphism becomes intolerable when it is > large enough to degrade rather than improve your signal-to-noise after > merging. > > For comparing maps, I'd say non-isomorphism becomes intolerable when the > difference peaks due to uninteresting movements becomes larger than those > due to interesting changes. What is interesting? Depends on what is > causing it. Large-scale domain motions due to laser-induced heat are > perhaps "not interesting" (to some), but large-scale domain motions due to > allosteric regulation are "interesting" (to some). Other "interesting" > things like ligand binding are an occupancy shift, which are traditionally > not considered non-isomorphism because the xyz positions aren't changing > (recall the definition of "isomorphous replacement"). The term > "non-isomorphism" is usually used to describe a large-scale positional > shift. > > These large-scale shifts are perhaps why changes in the unit cell can be > an indicator of isomorphism, but in my experience this relationship is > weak. This is especially true with serial crystallography where all three > cell dimensions are seldom constrained by a single image. That is, there > are sources of error that affect the accuracy of spot positions (measured > cell), but not the intensities (structure factors). So, my advice is to > take cell-based metrics of "isomorphism" with a grain of salt. > > It has already been pointed out that a pure scaling cell deformation (one > that preserves all the fractional coordinates of all the atoms) does not > change the structure factors. I would call such a pair of crystals > isomorphous. > > The origin of the cell-based rule of thumb quoted in Drenth is indeed the > 1956 paper by Crick and Magdoff that John Cooper shared. But I must stress: > their calculation, while groundbreaking, was incredibly simplistic. It was > equivalent to changing the header of a PDB file to a different unit cell, > leaving all the atoms at the same orthogonal x,y,z positions without regard > for crystal packing and non-bond clashes. The non-physical-ness of this > approach is perhaps why noone has ever re-visited it. It is also maximally > pessimistic, as real crystals are no doubt somewhere in between the harshly > rigid approximation of Crick & Magdoff and the perfectly soft elasticity > that yields no change in structure factors at all. > > To be fair, I suspect the computer used to do these calculations was > named Beatrice Magdoff. That is, in 1956 a "computer" was a job > description, not a device. Magdoff did some amazing things in her career, > and this one was no doubt a lot of work. I don't blame her and Crick for > trying to keep it simple. I would have done the same. I also suspect > Magdoff would agree that computers in 2024 are a bit more powerful than the > fastest computers of 1956. > > I expect in the coming year that barriers like non-isomorphism will start > to be overcome. No doubt borrowing from our cryo-EM friends who have been > stretching, pulling and sharpening 3D images for decades. > > Happy New Year everyone! > > -James Holton > MAD Scientist > > On 12/21/2023 11:37 AM, Tom Peat wrote: > > Hello All, > > I think Randy makes a very good point here- it depends on what you are > trying to do with your data sets. > If you are trying to merge them, 'isomorphous' is important for this to > work. If you are using them for cross crystal averaging, being less > isomorphous is better (more signal). > > James Holton has a story of Louise Johnson collecting data on lysozyme > (back in the 60's?) where she looked at one specific reflection to > determine whether the data sets she was collecting would be isomorphous and > scale. It turns out that although the cell was very similar, the > dehydration state of the crystal was very important for two lysozyme data > sets to scale together. The Rmerge for the two dehydration states was > something crazy large, like 44%, even though under the standard 'rules' > (more rules of thumb), one would have believed that these data sets should > have been 'isomorphous'. For the data sets that had the same dehydration > state, the data merged with 'typical' statistics of lysozyme (like 3-4%). > > James will have the details that I do not. > cheers, tom > -- > *From:* CCP4 bulletin board > on behalf of Randy John Read > > *Sent:* Thursday, December 21, 2023 10:53 PM > *To:* CCP4BB@JISCMAIL.AC.UK >
Re: [ccp4bb] what is isomorphous?
based metrics of "isomorphism" with a grain of salt. It has already been pointed out that a pure scaling cell deformation (one that preserves all the fractional coordinates of all the atoms) does not change the structure factors. I would call such a pair of crystals isomorphous. The origin of the cell-based rule of thumb quoted in Drenth is indeed the 1956 paper by Crick and Magdoff that John Cooper shared. But I must stress: their calculation, while groundbreaking, was incredibly simplistic. It was equivalent to changing the header of a PDB file to a different unit cell, leaving all the atoms at the same orthogonal x,y,z positions without regard for crystal packing and non-bond clashes. The non-physical-ness of this approach is perhaps why noone has ever re-visited it. It is also maximally pessimistic, as real crystals are no doubt somewhere in between the harshly rigid approximation of Crick & Magdoff and the perfectly soft elasticity that yields no change in structure factors at all. To be fair, I suspect the computer used to do these calculations was named Beatrice Magdoff. That is, in 1956 a "computer" was a job description, not a device. Magdoff did some amazing things in her career, and this one was no doubt a lot of work. I don't blame her and Crick for trying to keep it simple. I would have done the same. I also suspect Magdoff would agree that computers in 2024 are a bit more powerful than the fastest computers of 1956. I expect in the coming year that barriers like non-isomorphism will start to be overcome. No doubt borrowing from our cryo-EM friends who have been stretching, pulling and sharpening 3D images for decades. Happy New Year everyone! -James Holton MAD Scientist On 12/21/2023 11:37 AM, Tom Peat wrote: Hello All, I think Randy makes a very good point here- it depends on what you are trying to do with your data sets. If you are trying to merge them, 'isomorphous' is important for this to work. If you are using them for cross crystal averaging, being less isomorphous is better (more signal). James Holton has a story of Louise Johnson collecting data on lysozyme (back in the 60's?) where she looked at one specific reflection to determine whether the data sets she was collecting would be isomorphous and scale. It turns out that although the cell was very similar, the dehydration state of the crystal was very important for two lysozyme data sets to scale together. The Rmerge for the two dehydration states was something crazy large, like 44%, even though under the standard 'rules' (more rules of thumb), one would have believed that these data sets should have been 'isomorphous'. For the data sets that had the same dehydration state, the data merged with 'typical' statistics of lysozyme (like 3-4%). James will have the details that I do not. cheers, tom *From:* CCP4 bulletin board on behalf of Randy John Read *Sent:* Thursday, December 21, 2023 10:53 PM *To:* CCP4BB@JISCMAIL.AC.UK *Subject:* Re: [ccp4bb] what is isomorphous? [You don't often get email from rj...@cam.ac.uk. Learn why this is important at https://aka.ms/LearnAboutSenderIdentification ] I think we’ve strayed a bit from Doeke’s original question involving crystals A, B and C, where I think the consensus opinion would be that we would refer to crystal C as not being isomorphous to either A or B. On the question of what “isomorphous” means in the context of related crystals, I’m not sure we have complete consensus. I would tend to say that any two crystals are isomorphous if they have related unit cells and similar fractional coordinates of the atoms, so that (operationally) their diffraction patterns are correlated. However, there might be differences of opinion on whether two crystals can be considered isomorphous if one has exact crystallographic symmetry and the other has pseudosymmetry. (I would probably be on the more permissive side here.) In principle, I suppose being isomorphous (“same shape”) should be a binary decision, but in practice we’re interested in the implications of the degree to which perfect isomorphism is violated. So I would tend to use the term “poorly isomorphous” for a pair where the correlation between the diffraction patterns drops off well before the resolution limit. Crick was focused on percentage change in cell dimensions, but Bernhard is right that what matters is the ratio between the difference in cell lengths and the resolution of the data. It’s a bit counter-intuitive, but the effect of the difference between cell edges of 20 and 25 is the same as for cell edges of 200 and 205! By the way, the first time I learned this was from K. Cowtan and I hadn’t realised it’s also in Jan Drenth’s book. For isomorphous replacement (something some of us dimly remember from the days before AlphaFold), being poorly isomorph
Re: [ccp4bb] what is isomorphous?
Hello All, I think Randy makes a very good point here- it depends on what you are trying to do with your data sets. If you are trying to merge them, 'isomorphous' is important for this to work. If you are using them for cross crystal averaging, being less isomorphous is better (more signal). James Holton has a story of Louise Johnson collecting data on lysozyme (back in the 60's?) where she looked at one specific reflection to determine whether the data sets she was collecting would be isomorphous and scale. It turns out that although the cell was very similar, the dehydration state of the crystal was very important for two lysozyme data sets to scale together. The Rmerge for the two dehydration states was something crazy large, like 44%, even though under the standard 'rules' (more rules of thumb), one would have believed that these data sets should have been 'isomorphous'. For the data sets that had the same dehydration state, the data merged with 'typical' statistics of lysozyme (like 3-4%). James will have the details that I do not. cheers, tom From: CCP4 bulletin board on behalf of Randy John Read Sent: Thursday, December 21, 2023 10:53 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] what is isomorphous? [You don't often get email from rj...@cam.ac.uk. Learn why this is important at https://aka.ms/LearnAboutSenderIdentification ] I think we’ve strayed a bit from Doeke’s original question involving crystals A, B and C, where I think the consensus opinion would be that we would refer to crystal C as not being isomorphous to either A or B. On the question of what “isomorphous” means in the context of related crystals, I’m not sure we have complete consensus. I would tend to say that any two crystals are isomorphous if they have related unit cells and similar fractional coordinates of the atoms, so that (operationally) their diffraction patterns are correlated. However, there might be differences of opinion on whether two crystals can be considered isomorphous if one has exact crystallographic symmetry and the other has pseudosymmetry. (I would probably be on the more permissive side here.) In principle, I suppose being isomorphous (“same shape”) should be a binary decision, but in practice we’re interested in the implications of the degree to which perfect isomorphism is violated. So I would tend to use the term “poorly isomorphous” for a pair where the correlation between the diffraction patterns drops off well before the resolution limit. Crick was focused on percentage change in cell dimensions, but Bernhard is right that what matters is the ratio between the difference in cell lengths and the resolution of the data. It’s a bit counter-intuitive, but the effect of the difference between cell edges of 20 and 25 is the same as for cell edges of 200 and 205! By the way, the first time I learned this was from K. Cowtan and I hadn’t realised it’s also in Jan Drenth’s book. For isomorphous replacement (something some of us dimly remember from the days before AlphaFold), being poorly isomorphous is bad, but for cross-crystal averaging the more poorly isomorphous the better, because the molecular transform is being sampled in different places in reciprocal space. Best wishes, Randy Read > On 21 Dec 2023, at 10:53, Jon Cooper > <488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: > > Hello Harry, > > I think this is the paper you mean: > https://scripts.iucr.org/cgi-bin/paper?S0365110X56002552 > > They gave depressingly low estimates of how much the cell dimensions could > change in order for isomorphous replacement to still work. In reality, unit > cells can shrink and swell, but the fractional atomic coordinates remain > relatively unchanged (right?) so bigger unit cell differences still allow the > method to work. > > Best wishes, Jon Cooper. jon.b.coo...@protonmail.com > > Sent from Proton Mail mobile > > > > Original Message > On 21 Dec 2023, 09:07, Harry Powell < > 193323b1e616-dmarc-requ...@jiscmail.ac.uk> wrote: > Hi Didn’t Francis Crick have something to say about this in the early 1950s? > I’m sure it was published but off the top of my mind I can’t think where (one > of the more “established” members of this community will be able to give > chapter and verse)! If you want to read something a little more detailed than > people have mentioned here, there’s a “Methods in Enzymology” chapter by > Charlie Carter (?) et al from the early part of this century on the subject - > again, I can’t remember exactly who or when. Have a good break (which reminds > me to register for the CCP4 Study Weekend)! Harry > On 21 Dec 2023, at 08:04, > Tim Gruene wrote: > > Hi Doeke, > > you can take the coordinates of B and do > a rigid body refinement > against the
Re: [ccp4bb] what is isomorphous?
Thank you all. What I gather from this (please correct me) is: a. that for the intensities what matters is effectively whether s * delta_r is smaller than about 0.25--that is the fourier components at high resolution should not cover corresponding atoms that have shifted by more than about a quarter of the fourier component wavelength. (s=reciprocal lattice vector or S1-S0; delta_r is the coordinate shift) as these structure factors otherwise become uncorrelated. b. that as a result whether two things have "the same shape" (crystallographic isomorphism) depends on the level of spatial detail (resolution) one looks at. c. that the Drenth rule is very stringent--for two datasets to be considered isomorphous that they should be isomorphous up to the highest resolution, d. but that for other purposes (such as isomorphous replacement + rigid-body refinement) the bar is much lower, since low-resolution isomorphism can suffice. e. that in our example, A and B are apt to be "poorly isomorphous"--that is isomorphous, but not up to high resolution. f. following up on Marius' point--an implication seems to be that in some cases there is a high-resolution limit to which pairs of reflections meaningfully contribute to isomorphous difference maps, beyond which there no longer is an expectation for either the phases or amplitudes of two poorly isomorphous structures to be similar. Best wishes to all. Doeke -Original Message- From: CCP4 bulletin board On Behalf Of Randy John Read Sent: Thursday, December 21, 2023 6:53 AM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] what is isomorphous? I think we’ve strayed a bit from Doeke’s original question involving crystals A, B and C, where I think the consensus opinion would be that we would refer to crystal C as not being isomorphous to either A or B. On the question of what “isomorphous” means in the context of related crystals, I’m not sure we have complete consensus. I would tend to say that any two crystals are isomorphous if they have related unit cells and similar fractional coordinates of the atoms, so that (operationally) their diffraction patterns are correlated. However, there might be differences of opinion on whether two crystals can be considered isomorphous if one has exact crystallographic symmetry and the other has pseudosymmetry. (I would probably be on the more permissive side here.) In principle, I suppose being isomorphous (“same shape”) should be a binary decision, but in practice we’re interested in the implications of the degree to which perfect isomorphism is violated. So I would tend to use the term “poorly isomorphous” for a pair where the correlation between the diffraction patterns drops off well before the resolution limit. Crick was focused on percentage change in cell dimensions, but Bernhard is right that what matters is the ratio between the difference in cell lengths and the resolution of the data. It’s a bit counter-intuitive, but the effect of the difference between cell edges of 20 and 25 is the same as for cell edges of 200 and 205! By the way, the first time I learned this was from K. Cowtan and I hadn’t realised it’s also in Jan Drenth’s book. For isomorphous replacement (something some of us dimly remember from the days before AlphaFold), being poorly isomorphous is bad, but for cross-crystal averaging the more poorly isomorphous the better, because the molecular transform is being sampled in different places in reciprocal space. Best wishes, Randy Read > On 21 Dec 2023, at 10:53, Jon Cooper > <488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: > > Hello Harry, > > I think this is the paper you mean: > https://scripts.iucr.org/cgi-bin/paper?S0365110X56002552 > > They gave depressingly low estimates of how much the cell dimensions could > change in order for isomorphous replacement to still work. In reality, unit > cells can shrink and swell, but the fractional atomic coordinates remain > relatively unchanged (right?) so bigger unit cell differences still allow the > method to work. > > Best wishes, Jon Cooper. jon.b.coo...@protonmail.com > > Sent from Proton Mail mobile > > > > Original Message > On 21 Dec 2023, 09:07, Harry Powell < > 193323b1e616-dmarc-requ...@jiscmail.ac.uk> wrote: > Hi Didn’t Francis Crick have something to say about this in the early 1950s? > I’m sure it was published but off the top of my mind I can’t think where (one > of the more “established” members of this community will be able to give > chapter and verse)! If you want to read something a little more detailed than > people have mentioned here, there’s a “Methods in Enzymology” chapter by > Charlie Carter (?) et al from the early part of this century on the su
Re: [ccp4bb] what is isomorphous?
I think we’ve strayed a bit from Doeke’s original question involving crystals A, B and C, where I think the consensus opinion would be that we would refer to crystal C as not being isomorphous to either A or B. On the question of what “isomorphous” means in the context of related crystals, I’m not sure we have complete consensus. I would tend to say that any two crystals are isomorphous if they have related unit cells and similar fractional coordinates of the atoms, so that (operationally) their diffraction patterns are correlated. However, there might be differences of opinion on whether two crystals can be considered isomorphous if one has exact crystallographic symmetry and the other has pseudosymmetry. (I would probably be on the more permissive side here.) In principle, I suppose being isomorphous (“same shape”) should be a binary decision, but in practice we’re interested in the implications of the degree to which perfect isomorphism is violated. So I would tend to use the term “poorly isomorphous” for a pair where the correlation between the diffraction patterns drops off well before the resolution limit. Crick was focused on percentage change in cell dimensions, but Bernhard is right that what matters is the ratio between the difference in cell lengths and the resolution of the data. It’s a bit counter-intuitive, but the effect of the difference between cell edges of 20 and 25 is the same as for cell edges of 200 and 205! By the way, the first time I learned this was from K. Cowtan and I hadn’t realised it’s also in Jan Drenth’s book. For isomorphous replacement (something some of us dimly remember from the days before AlphaFold), being poorly isomorphous is bad, but for cross-crystal averaging the more poorly isomorphous the better, because the molecular transform is being sampled in different places in reciprocal space. Best wishes, Randy Read > On 21 Dec 2023, at 10:53, Jon Cooper > <488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: > > Hello Harry, > > I think this is the paper you mean: > https://scripts.iucr.org/cgi-bin/paper?S0365110X56002552 > > They gave depressingly low estimates of how much the cell dimensions could > change in order for isomorphous replacement to still work. In reality, unit > cells can shrink and swell, but the fractional atomic coordinates remain > relatively unchanged (right?) so bigger unit cell differences still allow the > method to work. > > Best wishes, Jon Cooper. jon.b.coo...@protonmail.com > > Sent from Proton Mail mobile > > > > Original Message > On 21 Dec 2023, 09:07, Harry Powell < > 193323b1e616-dmarc-requ...@jiscmail.ac.uk> wrote: > Hi Didn’t Francis Crick have something to say about this in the early 1950s? > I’m sure it was published but off the top of my mind I can’t think where (one > of the more “established” members of this community will be able to give > chapter and verse)! If you want to read something a little more detailed than > people have mentioned here, there’s a “Methods in Enzymology” chapter by > Charlie Carter (?) et al from the early part of this century on the subject - > again, I can’t remember exactly who or when. Have a good break (which reminds > me to register for the CCP4 Study Weekend)! Harry > On 21 Dec 2023, at 08:04, > Tim Gruene wrote: > > Hi Doeke, > > you can take the coordinates of B and do > a rigid body refinement > against the data from A. If this map is sufficient > to reproduce model A > (including model building and more refinement cycles), > then B is > isomorphous to A. You can do this the other way round, and the > result > may not be the same - hence, the mathematical definition of > isomorphous > is not identical to the practical use of 'isomorphous' > structures when > it comes to phasing. You can repeat this for each side of > the triangle > (each in two directions) in order to label the semantic > triangle. > > Merry Christmas, more peace on earth and sanity for the > elections in > 2024! > > Tim > > On Wed, 20 Dec 2023 20:15:17 + "Hekstra, > Doeke Romke" > wrote: > >> Dear colleagues, >> >> Something to muse over > during the holidays: >> >> Let's say we have three crystal forms of the same > protein, for >> example crystallized with different ligands. Crystal forms A > and B >> have the same crystal packing, except that one unit cell dimension > >> differs by, for example, 3%. Crystal form C has a different crystal >> > packing arrangement altogether. What is the right nomenclature to >> describe > the relationship between these crystal forms? >> >> If A and B are > sufficiently different that their phases are >> essentially uncorrelated, > what do we call them? Near-isomorphous? >> Non-isomorphous? Do we need a > different term to distinguish them from >> C or do we call all three datasets > non-isomorphous? >> >> Thanks for helping us resolve our semantic tangle. >> > >> Happy holidays! >> Doeke >>
Re: [ccp4bb] what is isomorphous?
Hello Harry, I think this is the paper you mean: https://scripts.iucr.org/cgi-bin/paper?S0365110X56002552 They gave depressingly low estimates of how much the cell dimensions could change in order for isomorphous replacement to still work. In reality, unit cells can shrink and swell, but the fractional atomic coordinates remain relatively unchanged (right?) so bigger unit cell differences still allow the method to work. Best wishes, Jon Cooper. jon.b.coo...@protonmail.com Sent from Proton Mail mobile Original Message On 21 Dec 2023, 09:07, Harry Powell wrote: > Hi Didn’t Francis Crick have something to say about this in the early 1950s? > I’m sure it was published but off the top of my mind I can’t think where (one > of the more “established” members of this community will be able to give > chapter and verse)! If you want to read something a little more detailed than > people have mentioned here, there’s a “Methods in Enzymology” chapter by > Charlie Carter (?) et al from the early part of this century on the subject - > again, I can’t remember exactly who or when. Have a good break (which reminds > me to register for the CCP4 Study Weekend)! Harry > On 21 Dec 2023, at 08:04, > Tim Gruene wrote: > > Hi Doeke, > > you can take the coordinates of B and do > a rigid body refinement > against the data from A. If this map is sufficient > to reproduce model A > (including model building and more refinement cycles), > then B is > isomorphous to A. You can do this the other way round, and the > result > may not be the same - hence, the mathematical definition of > isomorphous > is not identical to the practical use of 'isomorphous' > structures when > it comes to phasing. You can repeat this for each side of > the triangle > (each in two directions) in order to label the semantic > triangle. > > Merry Christmas, more peace on earth and sanity for the > elections in > 2024! > > Tim > > On Wed, 20 Dec 2023 20:15:17 + "Hekstra, > Doeke Romke" > wrote: > >> Dear colleagues, >> >> Something to muse over > during the holidays: >> >> Let's say we have three crystal forms of the same > protein, for >> example crystallized with different ligands. Crystal forms A > and B >> have the same crystal packing, except that one unit cell dimension > >> differs by, for example, 3%. Crystal form C has a different crystal >> > packing arrangement altogether. What is the right nomenclature to >> describe > the relationship between these crystal forms? >> >> If A and B are > sufficiently different that their phases are >> essentially uncorrelated, > what do we call them? Near-isomorphous? >> Non-isomorphous? Do we need a > different term to distinguish them from >> C or do we call all three datasets > non-isomorphous? >> >> Thanks for helping us resolve our semantic tangle. >> > >> Happy holidays! >> Doeke >> >> = >> >> Doeke Hekstra >> Assistant > Professor of Molecular & Cellular Biology, and of Applied >> Physics (SEAS), > Director of Undergraduate Studies, Chemical and >> Physical Biology Center > for Systems Biology, Harvard University >> 52 Oxford Street, NW311 >> > Cambridge, MA 02138 >> Office: 617-496-4740 >> Admin: 617-495-5651 (Lin Song) > >> >> >> >> > >> > >> To unsubscribe from the CCP4BB list, click the following link: >> > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 >> >> This > message was issued to members of www.jiscmail.ac.uk/CCP4BB, a >> mailing list > hosted by www.jiscmail.ac.uk, terms & conditions are >> available at > https://www.jiscmail.ac.uk/policyandsecurity/ > > > > -- > -- > Tim Gruene > > Head of the Centre for X-ray Structure Analysis > Faculty of Chemistry > > University of Vienna > > Phone: +43-1-4277-70202 > > GPG Key ID = A46BEE1A > > > > > > To unsubscribe from the CCP4BB list, click the following link: > > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 > > This > message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list > hosted by www.jiscmail.ac.uk, terms & conditions are available at > https://www.jiscmail.ac.uk/policyandsecurity/ > To > unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message > was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by > www.jiscmail.ac.uk, terms & conditions are available at > https://www.jiscmail.ac.uk/policyandsecurity/ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted
Re: [ccp4bb] what is isomorphous?
Hi Didn’t Francis Crick have something to say about this in the early 1950s? I’m sure it was published but off the top of my mind I can’t think where (one of the more “established” members of this community will be able to give chapter and verse)! If you want to read something a little more detailed than people have mentioned here, there’s a “Methods in Enzymology” chapter by Charlie Carter (?) et al from the early part of this century on the subject - again, I can’t remember exactly who or when. Have a good break (which reminds me to register for the CCP4 Study Weekend)! Harry > On 21 Dec 2023, at 08:04, Tim Gruene wrote: > > Hi Doeke, > > you can take the coordinates of B and do a rigid body refinement > against the data from A. If this map is sufficient to reproduce model A > (including model building and more refinement cycles), then B is > isomorphous to A. You can do this the other way round, and the result > may not be the same - hence, the mathematical definition of isomorphous > is not identical to the practical use of 'isomorphous' structures when > it comes to phasing. You can repeat this for each side of the triangle > (each in two directions) in order to label the semantic triangle. > > Merry Christmas, more peace on earth and sanity for the elections in > 2024! > > Tim > > On Wed, 20 Dec 2023 20:15:17 + "Hekstra, Doeke Romke" > wrote: > >> Dear colleagues, >> >> Something to muse over during the holidays: >> >> Let's say we have three crystal forms of the same protein, for >> example crystallized with different ligands. Crystal forms A and B >> have the same crystal packing, except that one unit cell dimension >> differs by, for example, 3%. Crystal form C has a different crystal >> packing arrangement altogether. What is the right nomenclature to >> describe the relationship between these crystal forms? >> >> If A and B are sufficiently different that their phases are >> essentially uncorrelated, what do we call them? Near-isomorphous? >> Non-isomorphous? Do we need a different term to distinguish them from >> C or do we call all three datasets non-isomorphous? >> >> Thanks for helping us resolve our semantic tangle. >> >> Happy holidays! >> Doeke >> >> = >> >> Doeke Hekstra >> Assistant Professor of Molecular & Cellular Biology, and of Applied >> Physics (SEAS), Director of Undergraduate Studies, Chemical and >> Physical Biology Center for Systems Biology, Harvard University >> 52 Oxford Street, NW311 >> Cambridge, MA 02138 >> Office:617-496-4740 >> Admin: 617-495-5651 (Lin Song) >> >> >> >> >> >> To unsubscribe from the CCP4BB list, click the following link: >> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 >> >> This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a >> mailing list hosted by www.jiscmail.ac.uk, terms & conditions are >> available at https://www.jiscmail.ac.uk/policyandsecurity/ > > > > -- > -- > Tim Gruene > Head of the Centre for X-ray Structure Analysis > Faculty of Chemistry > University of Vienna > > Phone: +43-1-4277-70202 > > GPG Key ID = A46BEE1A > > > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 > > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing > list hosted by www.jiscmail.ac.uk, terms & conditions are available at > https://www.jiscmail.ac.uk/policyandsecurity/ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] what is isomorphous?
Hi Doeke, you can take the coordinates of B and do a rigid body refinement against the data from A. If this map is sufficient to reproduce model A (including model building and more refinement cycles), then B is isomorphous to A. You can do this the other way round, and the result may not be the same - hence, the mathematical definition of isomorphous is not identical to the practical use of 'isomorphous' structures when it comes to phasing. You can repeat this for each side of the triangle (each in two directions) in order to label the semantic triangle. Merry Christmas, more peace on earth and sanity for the elections in 2024! Tim On Wed, 20 Dec 2023 20:15:17 + "Hekstra, Doeke Romke" wrote: > Dear colleagues, > > Something to muse over during the holidays: > > Let's say we have three crystal forms of the same protein, for > example crystallized with different ligands. Crystal forms A and B > have the same crystal packing, except that one unit cell dimension > differs by, for example, 3%. Crystal form C has a different crystal > packing arrangement altogether. What is the right nomenclature to > describe the relationship between these crystal forms? > > If A and B are sufficiently different that their phases are > essentially uncorrelated, what do we call them? Near-isomorphous? > Non-isomorphous? Do we need a different term to distinguish them from > C or do we call all three datasets non-isomorphous? > > Thanks for helping us resolve our semantic tangle. > > Happy holidays! > Doeke > > = > > Doeke Hekstra > Assistant Professor of Molecular & Cellular Biology, and of Applied > Physics (SEAS), Director of Undergraduate Studies, Chemical and > Physical Biology Center for Systems Biology, Harvard University > 52 Oxford Street, NW311 > Cambridge, MA 02138 > Office:617-496-4740 > Admin: 617-495-5651 (Lin Song) > > > > > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 > > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a > mailing list hosted by www.jiscmail.ac.uk, terms & conditions are > available at https://www.jiscmail.ac.uk/policyandsecurity/ -- -- Tim Gruene Head of the Centre for X-ray Structure Analysis Faculty of Chemistry University of Vienna Phone: +43-1-4277-70202 GPG Key ID = A46BEE1A To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/ pgp1Ya3oifqhO.pgp Description: OpenPGP digital signature
Re: [ccp4bb] what is isomorphous?
The Drenth rule of thumb makes sense. Whether 2 in the macromolecular sense isomorphous structures are isomorphous, is a matter or resolution, and it has to do with the reciprocal space overlap function aka G-function. So up to a certain resolution, 2 data sets may be isomorphous, but at high resolution, not anymore. In practical words, think of it in real space instead of FT reciprocal terms: to the myopic low-resolution eye, everything looks like a sphere and thus isomorphous. Just as in NCS, when you put on your high-resolution goggles, differences in real space (atom positions) become visible and the FT then becomes also non-isomorphous. In ML phasing, the non-isomorphism in essence pancakes your phasing probabilities due to increased variance. Result: The subtle art of data cut-off when exploiting isomorphism and shell-wise phase extension etc. Best, BR From: CCP4 bulletin board On Behalf Of Marius Schmidt Sent: Wednesday, December 20, 2023 14:36 To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] what is isomorphous? According to Jon, Isomorphous Replacement ALWAYS works, because it is only supposed to be isomorphous. Isomorphous difference maps can ALWAYS be calculated with sensible results, because the unit cells of the reference and the time-resolved data are only supposed to be isomorphous. Something is not right here... What is a "same unit cell?": unit cell params exact to the 6th digit, or maybe only to a fraction of the highest resolution, what fraction? Drenth says unit cells that differ by 0.25 x highest resolution can be considered isomorphous (0.5 A for 2 A data). What if 0.4 x highest resolution. Best Marius Marius Schmidt, Dr. rer. Nat. (habil.) Professor University of Wisconsin-Milwaukee Kenwood Interdisciplinary Research Complex Physics Department, Room 3087 3135 North Maryland Avenue Milwaukee, Wi 53211 phone (office): 1-414-229-4338 phone (lab): 414-229-3946 email: smar...@uwm.edu <mailto:smar...@uwm.edu> https://uwm.edu/physics/people/schmidt-marius/ https://sites.uwm.edu/smarius/ <https://www.bioxfel.org/> https://www.bioxfel.org/ Nature News and Views: https://www.nature.com/articles/d41586-023-00504-4 _ From: CCP4 bulletin board mailto:CCP4BB@JISCMAIL.AC.UK> > on behalf of Jon Cooper <488a26d62010-dmarc-requ...@jiscmail.ac.uk <mailto:488a26d62010-dmarc-requ...@jiscmail.ac.uk> > Sent: Wednesday, December 20, 2023 4:21 PM To: CCP4BB@JISCMAIL.AC.UK <mailto:CCP4BB@JISCMAIL.AC.UK> mailto:CCP4BB@JISCMAIL.AC.UK> > Subject: Re: [ccp4bb] what is isomorphous? Unless you have a degree in maths, the IUCr's "Little Dictionary of Crystallography" by A. Authier and G. Chapuis (2014) defies comprehension on this matter (it's all to do with set / group theory, I think, and there are many more morphisms covered in about 6 pages: homo, epi, mono, endo, auto). Having discussed this with Ian Tickle, about 10 or 12 years ago, the formal (?) definition of isomorphous simply means that the unit cells of two or more crystals are the same, but the structure/molecule/compound/mineral, etc, does not even have to be the same. A sensible definition for dumb biologists might be to say that A and B are isomorphous, but C isn't. Best wishes, Jon Cooper. jon.b.coo...@protonmail.com <mailto:jon.b.coo...@protonmail.com> Sent from Proton Mail mobile Original Message On 20 Dec 2023, 20:15, Hekstra, Doeke Romke < doeke_heks...@harvard.edu <mailto:doeke_heks...@harvard.edu> > wrote: Dear colleagues, Something to muse over during the holidays: Let’s say we have three crystal forms of the same protein, for example crystallized with different ligands. Crystal forms A and B have the same crystal packing, except that one unit cell dimension differs by, for example, 3%. Crystal form C has a different crystal packing arrangement altogether. What is the right nomenclature to describe the relationship between these crystal forms? If A and B are sufficiently different that their phases are essentially uncorrelated, what do we call them? Near-isomorphous? Non-isomorphous? Do we need a different term to distinguish them from C or do we call all three datasets non-isomorphous? Thanks for helping us resolve our semantic tangle. Happy holidays! Doeke = Doeke Hekstra Assistant Professor of Molecular & Cellular Biology, and of Applied Physics (SEAS), Director of Undergraduate Studies, Chemical and Physical Biology Center for Systems Biology, Harvard University 52 Oxford Street, NW311 Cambridge, MA 02138 Office:617-496-4740 Admin: 617-495-5651 (Lin Song) _ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB <https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1&g
Re: [ccp4bb] what is isomorphous?
According to Jon, Isomorphous Replacement ALWAYS works, because it is only supposed to be isomorphous. Isomorphous difference maps can ALWAYS be calculated with sensible results, because the unit cells of the reference and the time-resolved data are only supposed to be isomorphous. Something is not right here... What is a "same unit cell?": unit cell params exact to the 6th digit, or maybe only to a fraction of the highest resolution, what fraction? Drenth says unit cells that differ by 0.25 x highest resolution can be considered isomorphous (0.5 A for 2 A data). What if 0.4 x highest resolution. Best Marius Marius Schmidt, Dr. rer. Nat. (habil.) Professor University of Wisconsin-Milwaukee Kenwood Interdisciplinary Research Complex Physics Department, Room 3087 3135 North Maryland Avenue Milwaukee, Wi 53211 phone (office): 1-414-229-4338 phone (lab): 414-229-3946 email: smar...@uwm.edu https://uwm.edu/physics/people/schmidt-marius/ https://sites.uwm.edu/smarius/ https://www.bioxfel.org/ Nature News and Views: https://www.nature.com/articles/d41586-023-00504-4 From: CCP4 bulletin board on behalf of Jon Cooper <488a26d62010-dmarc-requ...@jiscmail.ac.uk> Sent: Wednesday, December 20, 2023 4:21 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] what is isomorphous? Unless you have a degree in maths, the IUCr's "Little Dictionary of Crystallography" by A. Authier and G. Chapuis (2014) defies comprehension on this matter (it's all to do with set / group theory, I think, and there are many more morphisms covered in about 6 pages: homo, epi, mono, endo, auto). Having discussed this with Ian Tickle, about 10 or 12 years ago, the formal (?) definition of isomorphous simply means that the unit cells of two or more crystals are the same, but the structure/molecule/compound/mineral, etc, does not even have to be the same. A sensible definition for dumb biologists might be to say that A and B are isomorphous, but C isn't. Best wishes, Jon Cooper. jon.b.coo...@protonmail.com Sent from Proton Mail mobile Original Message On 20 Dec 2023, 20:15, Hekstra, Doeke Romke < doeke_heks...@harvard.edu> wrote: Dear colleagues, Something to muse over during the holidays: Let’s say we have three crystal forms of the same protein, for example crystallized with different ligands. Crystal forms A and B have the same crystal packing, except that one unit cell dimension differs by, for example, 3%. Crystal form C has a different crystal packing arrangement altogether. What is the right nomenclature to describe the relationship between these crystal forms? If A and B are sufficiently different that their phases are essentially uncorrelated, what do we call them? Near-isomorphous? Non-isomorphous? Do we need a different term to distinguish them from C or do we call all three datasets non-isomorphous? Thanks for helping us resolve our semantic tangle. Happy holidays! Doeke = Doeke Hekstra Assistant Professor of Molecular & Cellular Biology, and of Applied Physics (SEAS), Director of Undergraduate Studies, Chemical and Physical Biology Center for Systems Biology, Harvard University 52 Oxford Street, NW311 Cambridge, MA 02138 Office:617-496-4740 Admin: 617-495-5651 (Lin Song) To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] what is isomorphous?
My apologies my second paragraph was badly wrong. What Ian Tickle said in 2008 (and to save him writing it all again ;-) is: "In general crystallographic usage 'isomorphous' refers to the similarity of crystal structures, i.e. same arrangement of atoms in the a.u. and the same symmetry. So strictly speaking, isomorphous crystals may have different cell parameters, so that NaCl and KCl are isomorphous (both being cubic with the same atomic arrangment), but the cell parameter of KCl is significantly greater than that of NaCl because the K ion is bigger. In MX 'isomorphous' usually implies both that the crystal form and structure are very similar and that the cell parameters are equal. It's perfectly possible that two crystals of completely different structures in the same space group accidentally have the same cell parameters, but clearly they would not be isomorphous, since the primary criterion is that the structures are similar. So it's not true to say by either definition that crystals are isomorphous if they have the same cell and symmetry, nor is it true that under this definition of isomorphism chemical similarity is a pre-requisite." "Rather the primary criterion of isomorphism is that the components that the structures have in common are not just similar but essentially identical (so the structures may have additional components that are not in common), and equality of symmetry and lattice parameters follow from this." On Wednesday, 20 December 2023 at 22:21, Jon Cooper <488a26d62010-dmarc-requ...@jiscmail.ac.uk> wrote: > Unless you have a degree in maths, the IUCr's "Little Dictionary of > Crystallography" by A. Authier and G. Chapuis (2014) defies comprehension on > this matter (it's all to do with set / group theory, I think, and there are > many more morphisms covered in about 6 pages: homo, epi, mono, endo, auto). > > Having discussed this with Ian Tickle, about 10 or 12 years ago, the formal > (?) definition of isomorphous simply means that the unit cells of two or more > crystals are the same, but the structure/molecule/compound/mineral, etc, does > not even have to be the same. A sensible definition for dumb biologists might > be to say that A and B are isomorphous, but C isn't. > > Best wishes, Jon Cooper. jon.b.coo...@protonmail.com > > Sent from Proton Mail mobile > > Original Message > On 20 Dec 2023, 20:15, Hekstra, Doeke Romke < doeke_heks...@harvard.edu> > wrote: > >> Dear colleagues, >> >> Something to muse over during the holidays: >> >> Let’s say we have three crystal forms of the same protein, for example >> crystallized with different ligands. Crystal forms A and B have the same >> crystal packing, except that one unit cell dimension differs by, for >> example, 3%. Crystal form C has a different crystal packing arrangement >> altogether. What is the right nomenclature to describe the relationship >> between these crystal forms? >> >> If A and B are sufficiently different that their phases are essentially >> uncorrelated, what do we call them? Near-isomorphous? Non-isomorphous? >> >> Do we need a different term to distinguish them from C or do we call all >> three datasets non-isomorphous? >> >> Thanks for helping us resolve our semantic tangle. >> >> Happy holidays! >> >> Doeke >> >> = >> >> Doeke Hekstra >> >> Assistant Professor of Molecular & Cellular Biology, and of Applied Physics >> (SEAS), >> >> Director of Undergraduate Studies, Chemical and Physical Biology >> >> Center for Systems Biology, Harvard University >> >> 52 Oxford Street, NW311 >> >> Cambridge, MA 02138 >> >> Office: 617-496-4740 >> >> Admin: 617-495-5651 (Lin Song) >> >> --- >> >> To unsubscribe from the CCP4BB list, click the following link: >> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 >> >> --- >> >> To unsubscribe from the CCP4BB list, click the following link: >> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
Re: [ccp4bb] what is isomorphous?
Unless you have a degree in maths, the IUCr's "Little Dictionary of Crystallography" by A. Authier and G. Chapuis (2014) defies comprehension on this matter (it's all to do with set / group theory, I think, and there are many more morphisms covered in about 6 pages: homo, epi, mono, endo, auto). Having discussed this with Ian Tickle, about 10 or 12 years ago, the formal (?) definition of isomorphous simply means that the unit cells of two or more crystals are the same, but the structure/molecule/compound/mineral, etc, does not even have to be the same. A sensible definition for dumb biologists might be to say that A and B are isomorphous, but C isn't. Best wishes, Jon Cooper. jon.b.coo...@protonmail.com Sent from Proton Mail mobile Original Message On 20 Dec 2023, 20:15, Hekstra, Doeke Romke wrote: > Dear colleagues, > > Something to muse over during the holidays: > > Let’s say we have three crystal forms of the same protein, for example > crystallized with different ligands. Crystal forms A and B have the same > crystal packing, except that one unit cell dimension differs by, for example, > 3%. Crystal form C has a different crystal packing arrangement altogether. > What is the right nomenclature to describe the relationship between these > crystal forms? > > If A and B are sufficiently different that their phases are essentially > uncorrelated, what do we call them? Near-isomorphous? Non-isomorphous? > > Do we need a different term to distinguish them from C or do we call all > three datasets non-isomorphous? > > Thanks for helping us resolve our semantic tangle. > > Happy holidays! > > Doeke > > = > > Doeke Hekstra > > Assistant Professor of Molecular & Cellular Biology, and of Applied Physics > (SEAS), > > Director of Undergraduate Studies, Chemical and Physical Biology > > Center for Systems Biology, Harvard University > > 52 Oxford Street, NW311 > > Cambridge, MA 02138 > > Office: 617-496-4740 > > Admin: 617-495-5651 (Lin Song) > > --- > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
