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 data from A. If this map is sufficient > to reproduce model A > (including model building and more refinement cycles), > then B is >
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 subject - > again, I can’t remember exactly who or when. Have a good break (which reminds > me to register for the CCP4
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
