Re: [ccp4bb] Chiral volume outliers SO4
I'm very happy to get to the bottom of this and get it fixed. I do wonder if it had become over parametrised. Cheers Joel -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Robbie Joosten Sent: Thursday, 12 July 2012 12:16 a.m. To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Hi Ian, @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). But this is only because the 'negative' volume sign was erroneously used in the chiral restraint instead of 'both' (or better still IMO no chiral restraint at all), right? If so I don't find it surprising at all that Refmac tried to flip the sulphate and ended up flattening it. Seems to be a good illustration of the GIGO (garbage in - garbage out) principle. Just because the garbage input in this case is in the official CCP4 distribution and not (as is of course more commonly the case) perpetrated by the user doesn't make it any less garbage. The problem is that in the creation of chiral volume targets chemically equivalent (groups of) atoms are not recognized as such. So any new or recreated restraint files will have either 'positiv' or 'negativ' and the problem starts all over again. That is why it is better to stay consistent and choose one chirality (the same one as in the 'ideal' coordinates in the PDB ligand descriptions). This will also make it easier compare ligands after aligning them (this applies to ligands more complex than sulfate). Obviously, users should not be forced to deal with these things. Programs like Refmac and COOT should fix chiral volume inversions for the user, because it is only relevant inside the computer. That is the idea of chiron, just fix these 'problems' automatically by swapping equivalent atoms whenever Refmac gives a chiral volume inversion warning. It should make life a bit easier. The point I was making is that in this and similar cases you don't need a chiral restraint at all: surely 4 bond lengths and 6 bond angles define the chiral volume pretty well already? Or are there cases where without a chiral restraint the refinement still tries to flip the chirality (I would fine that hard to believe). I agree with you for sulfate, and also for phosphate ;). I don't know what happens in other compounds at poor resolution, when bond and angle targets (and their SDs) are not equivalent. I guess that some angle might 'give way' before others. That is something that should be tested. I have a growing list of chiral centers that have this problem if you are interested. Cheers, Robbie - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP/+M0UxlJ7aRr7hoRAvcqAJ9nuBmSmc2qVyMf17T76stvbqmfEQCfQIDo v9xoSL/c7LGAKFe3B5Rk9Zc= =PSch -END PGP SIGNATURE-
Re: [ccp4bb] Chiral volume outliers SO4
On Sunday, 15 July 2012, Dale Tronrud wrote: There are good reasons for maintaining order in this human-induced numbering scheme. A common operation is to superimpose two molecules and calculate the rmsd of the positional differences. This calculation is not useful when the Val CG1 and CG2 are swapped in one molecule relative to the other. Suddenly you have, maybe a handful, of atoms that differ in position by about 3.5 A when most of us would consider this to be nonsense. We want the rmsd between equivalent atoms regardless of the human-induced numbering scheme. There are two ways this can come about. 1) The overlay program could swap the labels on one to match the other or 2) The labels can be defined to be consistent from the start. 3) The closest-to-superimposed atoms could be paired regardless of their labels 4) Chemically equivalent atoms could be given the same name, which is then not unique but allows it to match any other atoms with the same name I'd normally choose (3) in practice, because it's the only method that works reliably without universal agreement going forward and universal remediation looking backward. cheers, Ethan
Re: [ccp4bb] Chiral volume outliers SO4
-BEGIN PGP SIGNED MESSAGE- Hash: SHA1 Dear all, I am surprised by the discussion about chiraliy of an utterly centrosymmetric molecule. Shouldn't the four Oxygen atoms be at least from a QM point-of-view to indistinguishable? What reason is there to maintain a certain 'order' in the human-induced numbering scheme? Cheers, Tim On 07/13/12 00:22, Dale Tronrud wrote: While this change has made your symptom go away it is stretching it a bit to call this a fix. You have not corrected the root problem that the names you have given your atoms do not match the convention which is being applied for SO4 groups. Changing the cif means that you don't have to worry about it, but people who study such details will be forced to deal with the incorrect labels of your model in the future. Wouldn't it just be easier to swap the names of two oxygen atoms in each SO4, leaving the cif alone? Your difficulties will go away and people using your model in the future will also have a simpler life. This labeling problem is not new. The fight to standardize the labeling of the methyl groups in Valine and Leucine was raging in the 1980's. Standardizing the labels on the PO4 groups in DNA/RNA was much more recent. It helps everyone when you know you can overlay two models and have a logical solution without a rotation matrix with a determinate of -1. Besides, you will continue to be bitten by this problem as you use other programs, until you actually swap some labels. Dale Tronrud On 07/12/12 15:00, Joel Tyndall wrote: Hi all, Thanks very much to all who responded so quickly. The fix is a one liner in the SO4.cif file (last line) SO4 chir_01 S O1 O2 O3both which I believe is now in the 6.3.0 release. Interestingly the chirality parameters were not in the SO4.cif file in 6.1.3 but then appeared in 6.2.0. Once again I'm very happy to get to the bottom of this and get it fixed. I do wonder if it had become over parametrised. Cheers Joel -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Robbie Joosten Sent: Thursday, 12 July 2012 12:16 a.m. To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Hi Ian, @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). But this is only because the 'negative' volume sign was erroneously used in the chiral restraint instead of 'both' (or better still IMO no chiral restraint at all), right? If so I don't find it surprising at all that Refmac tried to flip the sulphate and ended up flattening it. Seems to be a good illustration of the GIGO (garbage in - garbage out) principle. Just because the garbage input in this case is in the official CCP4 distribution and not (as is of course more commonly the case) perpetrated by the user doesn't make it any less garbage. The problem is that in the creation of chiral volume targets chemically equivalent (groups of) atoms are not recognized as such. So any new or recreated restraint files will have either 'positiv' or 'negativ' and the problem starts all over again. That is why it is better to stay consistent and choose one chirality (the same one as in the 'ideal' coordinates in the PDB ligand descriptions). This will also make it easier compare ligands after aligning them (this applies to ligands more complex than sulfate). Obviously, users should not be forced to deal with these things. Programs like Refmac and COOT should fix chiral volume inversions for the user, because it is only relevant inside the computer. That is the idea of chiron, just fix these 'problems' automatically by swapping equivalent atoms whenever Refmac gives a chiral volume inversion warning. It should make life a bit easier. The point I was making is that in this and similar cases you don't need a chiral restraint at all: surely 4 bond lengths and 6 bond angles define the chiral volume pretty well already? Or are there cases where without a chiral restraint the refinement still tries to flip the chirality (I would fine that hard to believe). I agree with you for sulfate, and also for phosphate ;). I don't know what happens in other compounds at poor resolution, when bond and angle targets (and their SDs) are not equivalent. I guess that some angle might 'give way' before others. That is something that should be tested. I have a growing list of chiral centers that have this problem if you are interested. Cheers, Robbie - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP/+M0UxlJ7aRr7hoRAvcqAJ9nuBmSmc2qVyMf17T76stvbqmfEQCfQIDo v9xoSL/c7LGAKFe3B5Rk9Zc
Re: [ccp4bb] Chiral volume outliers SO4
Dear All, I'm with Dale on this one. It's better to have a standard and roll with it, than allow for ambiguity. The discussion just happened to start with a rather silly example as Tim pointed out. The ligand 1N1 (http://ligand-expo.rcsb.org/reports/1/1N1/1N1_D3L1.gif) is a better example: The atoms N5 and N6 can have inverted chirality. If it is just one of the two, then the molecule is distorted (IFF the restraint file is correct!). If both have inverted chirality than the problem can be fixed by label swapping. Hacking the restraint file to allow both positive and negative chirality would allow you to distort the molecule. Cheers, Robbie -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Tim Gruene Sent: Friday, July 13, 2012 10:59 To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 Dear all, I am surprised by the discussion about chiraliy of an utterly centrosymmetric molecule. Shouldn't the four Oxygen atoms be at least from a QM point-of-view to indistinguishable? What reason is there to maintain a certain 'order' in the human-induced numbering scheme? Cheers, Tim On 07/13/12 00:22, Dale Tronrud wrote: While this change has made your symptom go away it is stretching it a bit to call this a fix. You have not corrected the root problem that the names you have given your atoms do not match the convention which is being applied for SO4 groups. Changing the cif means that you don't have to worry about it, but people who study such details will be forced to deal with the incorrect labels of your model in the future. Wouldn't it just be easier to swap the names of two oxygen atoms in each SO4, leaving the cif alone? Your difficulties will go away and people using your model in the future will also have a simpler life. This labeling problem is not new. The fight to standardize the labeling of the methyl groups in Valine and Leucine was raging in the 1980's. Standardizing the labels on the PO4 groups in DNA/RNA was much more recent. It helps everyone when you know you can overlay two models and have a logical solution without a rotation matrix with a determinate of -1. Besides, you will continue to be bitten by this problem as you use other programs, until you actually swap some labels. Dale Tronrud On 07/12/12 15:00, Joel Tyndall wrote: Hi all, Thanks very much to all who responded so quickly. The fix is a one liner in the SO4.cif file (last line) SO4 chir_01 S O1 O2 O3both which I believe is now in the 6.3.0 release. Interestingly the chirality parameters were not in the SO4.cif file in 6.1.3 but then appeared in 6.2.0. Once again I'm very happy to get to the bottom of this and get it fixed. I do wonder if it had become over parametrised. Cheers Joel -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Robbie Joosten Sent: Thursday, 12 July 2012 12:16 a.m. To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Hi Ian, @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). But this is only because the 'negative' volume sign was erroneously used in the chiral restraint instead of 'both' (or better still IMO no chiral restraint at all), right? If so I don't find it surprising at all that Refmac tried to flip the sulphate and ended up flattening it. Seems to be a good illustration of the GIGO (garbage in - garbage out) principle. Just because the garbage input in this case is in the official CCP4 distribution and not (as is of course more commonly the case) perpetrated by the user doesn't make it any less garbage. The problem is that in the creation of chiral volume targets chemically equivalent (groups of) atoms are not recognized as such. So any new or recreated restraint files will have either 'positiv' or 'negativ' and the problem starts all over again. That is why it is better to stay consistent and choose one chirality (the same one as in the 'ideal' coordinates in the PDB ligand descriptions). This will also make it easier compare ligands after aligning them (this applies to ligands more complex than sulfate). Obviously, users should not be forced to deal with these things. Programs like Refmac and COOT should fix chiral volume inversions for the user, because it is only relevant inside the computer. That is the idea of chiron, just fix these 'problems' automatically by swapping equivalent atoms whenever Refmac gives a chiral volume inversion warning. It should make life a bit easier. The point I was making is that in this and similar cases you don't need a chiral restraint at all: surely 4
Re: [ccp4bb] Chiral volume outliers SO4
Dear Robbie and ccp4bb, Is 1N1 not a different type of problem though, where a chirality restraint is valid and so the atom labelling is important? Are you saying that we should always use the cif dictionary, even when there are errors? Surely in the SO4 case, as Ian said, it is better to remove the unnecessary restraint altogether. The sulphate cif file seems to have had this bug introduced in the current CCP4 version. Andrew On Fri, 2012-07-13 at 12:54 +0200, Robbie Joosten wrote: Dear All, I'm with Dale on this one. It's better to have a standard and roll with it, than allow for ambiguity. The discussion just happened to start with a rather silly example as Tim pointed out. The ligand 1N1 (http://ligand-expo.rcsb.org/reports/1/1N1/1N1_D3L1.gif) is a better example: The atoms N5 and N6 can have inverted chirality. If it is just one of the two, then the molecule is distorted (IFF the restraint file is correct!). If both have inverted chirality than the problem can be fixed by label swapping. Hacking the restraint file to allow both positive and negative chirality would allow you to distort the molecule. Cheers, Robbie -- Andrew Purkiss X-ray Laboratory London Research Institute Cancer Research UK
Re: [ccp4bb] Chiral volume outliers SO4
Hi Andrew, Indeed, provided the atom labeling is correct the chiral volume restraint actually says whether the groups on the ring a axial or equatorial. The cif files do not define that any other way, so without the restraint the description of the molecule is ambiguous. Note that the chirality restraint only describes the hand, the actual chiral volume is calculated from the angle restraints. In the more general case I think people are talking different languages. There is chemical chirality (the real deal) and computational chirality. In refinement and structure comparison the latter does matter (again, see Dale's post). Problems with restraints are one of the reasons why there are relatively many problems with ligands in the PDB (e.g. http://www.springerlink.com/content/eu28538101v7v885/). Cheers, Robbie -Original Message- From: Andrew Purkiss [mailto:a.purk...@mail.cryst.bbk.ac.uk] Sent: Friday, July 13, 2012 14:09 To: Robbie Joosten Cc: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Dear Robbie and ccp4bb, Is 1N1 not a different type of problem though, where a chirality restraint is valid and so the atom labelling is important? Are you saying that we should always use the cif dictionary, even when there are errors? Surely in the SO4 case, as Ian said, it is better to remove the unnecessary restraint altogether. The sulphate cif file seems to have had this bug introduced in the current CCP4 version. Andrew On Fri, 2012-07-13 at 12:54 +0200, Robbie Joosten wrote: Dear All, I'm with Dale on this one. It's better to have a standard and roll with it, than allow for ambiguity. The discussion just happened to start with a rather silly example as Tim pointed out. The ligand 1N1 (http://ligand-expo.rcsb.org/reports/1/1N1/1N1_D3L1.gif) is a better example: The atoms N5 and N6 can have inverted chirality. If it is just one of the two, then the molecule is distorted (IFF the restraint file is correct!). If both have inverted chirality than the problem can be fixed by label swapping. Hacking the restraint file to allow both positive and negative chirality would allow you to distort the molecule. Cheers, Robbie -- Andrew Purkiss X-ray Laboratory London Research Institute Cancer Research UK
Re: [ccp4bb] Chiral volume outliers SO4
Hi Robbie, Interesting! In the article you referred to there isn't a single mention of the word chiral or its derivatives. They talk more about strained ligands, a problem which is addressed by the Grade operation and similar tools, and wrong geometry altogether, which we all agree should be cured. As Ian pointed out computational chirality (Pasteur must be spinning in his grave right now) is addressed nicely in the cif file (chirality both). My 2p. Boaz Boaz Shaanan, Ph.D. Dept. of Life Sciences Ben-Gurion University of the Negev Beer-Sheva 84105 Israel E-mail: bshaa...@bgu.ac.il Phone: 972-8-647-2220 Skype: boaz.shaanan Fax: 972-8-647-2992 or 972-8-646-1710 From: CCP4 bulletin board [CCP4BB@JISCMAIL.AC.UK] on behalf of Robbie Joosten [robbie_joos...@hotmail.com] Sent: Friday, July 13, 2012 5:18 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Hi Andrew, Indeed, provided the atom labeling is correct the chiral volume restraint actually says whether the groups on the ring a axial or equatorial. The cif files do not define that any other way, so without the restraint the description of the molecule is ambiguous. Note that the chirality restraint only describes the hand, the actual chiral volume is calculated from the angle restraints. In the more general case I think people are talking different languages. There is chemical chirality (the real deal) and computational chirality. In refinement and structure comparison the latter does matter (again, see Dale's post). Problems with restraints are one of the reasons why there are relatively many problems with ligands in the PDB (e.g. http://www.springerlink.com/content/eu28538101v7v885/). Cheers, Robbie -Original Message- From: Andrew Purkiss [mailto:a.purk...@mail.cryst.bbk.ac.uk] Sent: Friday, July 13, 2012 14:09 To: Robbie Joosten Cc: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Dear Robbie and ccp4bb, Is 1N1 not a different type of problem though, where a chirality restraint is valid and so the atom labelling is important? Are you saying that we should always use the cif dictionary, even when there are errors? Surely in the SO4 case, as Ian said, it is better to remove the unnecessary restraint altogether. The sulphate cif file seems to have had this bug introduced in the current CCP4 version. Andrew On Fri, 2012-07-13 at 12:54 +0200, Robbie Joosten wrote: Dear All, I'm with Dale on this one. It's better to have a standard and roll with it, than allow for ambiguity. The discussion just happened to start with a rather silly example as Tim pointed out. The ligand 1N1 (http://ligand-expo.rcsb.org/reports/1/1N1/1N1_D3L1.gif) is a better example: The atoms N5 and N6 can have inverted chirality. If it is just one of the two, then the molecule is distorted (IFF the restraint file is correct!). If both have inverted chirality than the problem can be fixed by label swapping. Hacking the restraint file to allow both positive and negative chirality would allow you to distort the molecule. Cheers, Robbie -- Andrew Purkiss X-ray Laboratory London Research Institute Cancer Research UK
Re: [ccp4bb] Chiral volume outliers SO4
Hi all, Thanks very much to all who responded so quickly. The fix is a one liner in the SO4.cif file (last line) SO4 chir_01 S O1 O2 O3both which I believe is now in the 6.3.0 release. Interestingly the chirality parameters were not in the SO4.cif file in 6.1.3 but then appeared in 6.2.0. Once again I'm very happy to get to the bottom of this and get it fixed. I do wonder if it had become over parametrised. Cheers Joel -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Robbie Joosten Sent: Thursday, 12 July 2012 12:16 a.m. To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Hi Ian, @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). But this is only because the 'negative' volume sign was erroneously used in the chiral restraint instead of 'both' (or better still IMO no chiral restraint at all), right? If so I don't find it surprising at all that Refmac tried to flip the sulphate and ended up flattening it. Seems to be a good illustration of the GIGO (garbage in - garbage out) principle. Just because the garbage input in this case is in the official CCP4 distribution and not (as is of course more commonly the case) perpetrated by the user doesn't make it any less garbage. The problem is that in the creation of chiral volume targets chemically equivalent (groups of) atoms are not recognized as such. So any new or recreated restraint files will have either 'positiv' or 'negativ' and the problem starts all over again. That is why it is better to stay consistent and choose one chirality (the same one as in the 'ideal' coordinates in the PDB ligand descriptions). This will also make it easier compare ligands after aligning them (this applies to ligands more complex than sulfate). Obviously, users should not be forced to deal with these things. Programs like Refmac and COOT should fix chiral volume inversions for the user, because it is only relevant inside the computer. That is the idea of chiron, just fix these 'problems' automatically by swapping equivalent atoms whenever Refmac gives a chiral volume inversion warning. It should make life a bit easier. The point I was making is that in this and similar cases you don't need a chiral restraint at all: surely 4 bond lengths and 6 bond angles define the chiral volume pretty well already? Or are there cases where without a chiral restraint the refinement still tries to flip the chirality (I would fine that hard to believe). I agree with you for sulfate, and also for phosphate ;). I don't know what happens in other compounds at poor resolution, when bond and angle targets (and their SDs) are not equivalent. I guess that some angle might 'give way' before others. That is something that should be tested. I have a growing list of chiral centers that have this problem if you are interested. Cheers, Robbie
Re: [ccp4bb] Chiral volume outliers SO4
While this change has made your symptom go away it is stretching it a bit to call this a fix. You have not corrected the root problem that the names you have given your atoms do not match the convention which is being applied for SO4 groups. Changing the cif means that you don't have to worry about it, but people who study such details will be forced to deal with the incorrect labels of your model in the future. Wouldn't it just be easier to swap the names of two oxygen atoms in each SO4, leaving the cif alone? Your difficulties will go away and people using your model in the future will also have a simpler life. This labeling problem is not new. The fight to standardize the labeling of the methyl groups in Valine and Leucine was raging in the 1980's. Standardizing the labels on the PO4 groups in DNA/RNA was much more recent. It helps everyone when you know you can overlay two models and have a logical solution without a rotation matrix with a determinate of -1. Besides, you will continue to be bitten by this problem as you use other programs, until you actually swap some labels. Dale Tronrud On 07/12/12 15:00, Joel Tyndall wrote: Hi all, Thanks very much to all who responded so quickly. The fix is a one liner in the SO4.cif file (last line) SO4 chir_01 S O1 O2 O3both which I believe is now in the 6.3.0 release. Interestingly the chirality parameters were not in the SO4.cif file in 6.1.3 but then appeared in 6.2.0. Once again I'm very happy to get to the bottom of this and get it fixed. I do wonder if it had become over parametrised. Cheers Joel -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Robbie Joosten Sent: Thursday, 12 July 2012 12:16 a.m. To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Hi Ian, @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). But this is only because the 'negative' volume sign was erroneously used in the chiral restraint instead of 'both' (or better still IMO no chiral restraint at all), right? If so I don't find it surprising at all that Refmac tried to flip the sulphate and ended up flattening it. Seems to be a good illustration of the GIGO (garbage in - garbage out) principle. Just because the garbage input in this case is in the official CCP4 distribution and not (as is of course more commonly the case) perpetrated by the user doesn't make it any less garbage. The problem is that in the creation of chiral volume targets chemically equivalent (groups of) atoms are not recognized as such. So any new or recreated restraint files will have either 'positiv' or 'negativ' and the problem starts all over again. That is why it is better to stay consistent and choose one chirality (the same one as in the 'ideal' coordinates in the PDB ligand descriptions). This will also make it easier compare ligands after aligning them (this applies to ligands more complex than sulfate). Obviously, users should not be forced to deal with these things. Programs like Refmac and COOT should fix chiral volume inversions for the user, because it is only relevant inside the computer. That is the idea of chiron, just fix these 'problems' automatically by swapping equivalent atoms whenever Refmac gives a chiral volume inversion warning. It should make life a bit easier. The point I was making is that in this and similar cases you don't need a chiral restraint at all: surely 4 bond lengths and 6 bond angles define the chiral volume pretty well already? Or are there cases where without a chiral restraint the refinement still tries to flip the chirality (I would fine that hard to believe). I agree with you for sulfate, and also for phosphate ;). I don't know what happens in other compounds at poor resolution, when bond and angle targets (and their SDs) are not equivalent. I guess that some angle might 'give way' before others. That is something that should be tested. I have a growing list of chiral centers that have this problem if you are interested. Cheers, Robbie
Re: [ccp4bb] Chiral volume outliers SO4
Hi Dale, Thanks for the input. I guess as a relatively transient user I am not appreciating the depth of the problem. However, by at least raising this issue, I'm hoping that the fight can be sorted out. Where does my sulfate problem stem from? Is it from importing the fragment in COOT? Is it the actual cif file which is read by COOT? As noted, software updates tend to be quicker than we can refine our structures (That albeit is relatively slow on our behalf). I am all for standardisation, but in the long run (at least for me) the sulfate(s) becomes a minor part of the structures. I'll look at swapping the oxygens in the SO4's. Cheers Joel -Original Message- From: Dale Tronrud [mailto:det...@uoxray.uoregon.edu] Sent: Friday, 13 July 2012 10:22 a.m. To: Joel Tyndall Cc: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 While this change has made your symptom go away it is stretching it a bit to call this a fix. You have not corrected the root problem that the names you have given your atoms do not match the convention which is being applied for SO4 groups. Changing the cif means that you don't have to worry about it, but people who study such details will be forced to deal with the incorrect labels of your model in the future. Wouldn't it just be easier to swap the names of two oxygen atoms in each SO4, leaving the cif alone? Your difficulties will go away and people using your model in the future will also have a simpler life. This labeling problem is not new. The fight to standardize the labeling of the methyl groups in Valine and Leucine was raging in the 1980's. Standardizing the labels on the PO4 groups in DNA/RNA was much more recent. It helps everyone when you know you can overlay two models and have a logical solution without a rotation matrix with a determinate of -1. Besides, you will continue to be bitten by this problem as you use other programs, until you actually swap some labels. Dale Tronrud On 07/12/12 15:00, Joel Tyndall wrote: Hi all, Thanks very much to all who responded so quickly. The fix is a one liner in the SO4.cif file (last line) SO4 chir_01 S O1 O2 O3both which I believe is now in the 6.3.0 release. Interestingly the chirality parameters were not in the SO4.cif file in 6.1.3 but then appeared in 6.2.0. Once again I'm very happy to get to the bottom of this and get it fixed. I do wonder if it had become over parametrised. Cheers Joel -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Robbie Joosten Sent: Thursday, 12 July 2012 12:16 a.m. To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Hi Ian, @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). But this is only because the 'negative' volume sign was erroneously used in the chiral restraint instead of 'both' (or better still IMO no chiral restraint at all), right? If so I don't find it surprising at all that Refmac tried to flip the sulphate and ended up flattening it. Seems to be a good illustration of the GIGO (garbage in - garbage out) principle. Just because the garbage input in this case is in the official CCP4 distribution and not (as is of course more commonly the case) perpetrated by the user doesn't make it any less garbage. The problem is that in the creation of chiral volume targets chemically equivalent (groups of) atoms are not recognized as such. So any new or recreated restraint files will have either 'positiv' or 'negativ' and the problem starts all over again. That is why it is better to stay consistent and choose one chirality (the same one as in the 'ideal' coordinates in the PDB ligand descriptions). This will also make it easier compare ligands after aligning them (this applies to ligands more complex than sulfate). Obviously, users should not be forced to deal with these things. Programs like Refmac and COOT should fix chiral volume inversions for the user, because it is only relevant inside the computer. That is the idea of chiron, just fix these 'problems' automatically by swapping equivalent atoms whenever Refmac gives a chiral volume inversion warning. It should make life a bit easier. The point I was making is that in this and similar cases you don't need a chiral restraint at all: surely 4 bond lengths and 6 bond angles define the chiral volume pretty well already? Or are there cases where without a chiral restraint the refinement still tries to flip the chirality (I would fine that hard to believe). I agree with you for sulfate, and also for phosphate ;). I don't know what happens in other compounds at poor resolution, when bond and angle targets (and their SDs) are not equivalent. I guess that some
Re: [ccp4bb] Chiral volume outliers SO4
-BEGIN PGP SIGNED MESSAGE- Hash: SHA1 Dear Joel, out of curiosity: what is the Chiral volume outliers issue? Cheers, Tim On 07/11/12 01:00, Joel Tyndall wrote: Hi people, We are refining a structure with sulfates and we are getting the Chiral volume outliers issue. I understand the problem as being computational where the oxygens are in reality equivalent but computationally named differently. I have seen the recent Acta Cryst D paper (April 2012 - PDB_REDO) which talks about this issue and mentions the development of Chiron which could fix this issue. Is there a way to fix this problem using existing tools (or editing). We have ~20 sulfates in our protein (10-mer system) Thanks heaps Joel _ Joel Tyndall, PhD Senior Lecturer in Medicinal Chemistry National School of Pharmacy University of Otago PO Box 56 Dunedin 9054 New Zealand Skype: jtyndall Ph: +64 3 479 7293 - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP/U5+UxlJ7aRr7hoRAqaUAKD4Eo2tqarIwbK6+mHIfYYHcyhAKQCgy02F XK8ZYLNW3gI873nrtkZSv9E= =ishS -END PGP SIGNATURE-
Re: [ccp4bb] Chiral volume outliers SO4
Well - the problem may well be here - in the REFMAC dictionary (see $CLIBD/monomers.s.SO4.cif ) the chiral volume calculation uses at the order of the O numbering around the S atom . So if your O numbering is not right handed you will have the chiral volume calculated as positive, not negative. There are various fixes. Edit the SO4 and just the numbering of 2 of the O atoms - eg use labels: S O2 O1 O3 Or edit the SO4.cif to have SO4 chir_01 S O1 O2 O3both Eleanor loop_ _chem_comp_chir.comp_id _chem_comp_chir.id _chem_comp_chir.atom_id_centre _chem_comp_chir.atom_id_1 _chem_comp_chir.atom_id_2 _chem_comp_chir.atom_id_3 _chem_comp_chir.volume_sign SO4 chir_01 S O1 O2 O3negativ On 11 July 2012 10:59, Tim Gruene t...@shelx.uni-ac.gwdg.de wrote: -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 Dear Joel, out of curiosity: what is the Chiral volume outliers issue? Cheers, Tim On 07/11/12 01:00, Joel Tyndall wrote: Hi people, We are refining a structure with sulfates and we are getting the Chiral volume outliers issue. I understand the problem as being computational where the oxygens are in reality equivalent but computationally named differently. I have seen the recent Acta Cryst D paper (April 2012 - PDB_REDO) which talks about this issue and mentions the development of Chiron which could fix this issue. Is there a way to fix this problem using existing tools (or editing). We have ~20 sulfates in our protein (10-mer system) Thanks heaps Joel _ Joel Tyndall, PhD Senior Lecturer in Medicinal Chemistry National School of Pharmacy University of Otago PO Box 56 Dunedin 9054 New Zealand Skype: jtyndall Ph: +64 3 479 7293 - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP/U5+UxlJ7aRr7hoRAqaUAKD4Eo2tqarIwbK6+mHIfYYHcyhAKQCgy02F XK8ZYLNW3gI873nrtkZSv9E= =ishS -END PGP SIGNATURE-
Re: [ccp4bb] Chiral volume outliers SO4
Hi Joel, I prefer the swapping of atom names, which is pretty much what the program chiron does, over hacking the restraint file. The latter makes the problem reappear as soon as you use your PDB file on a machine with an 'unhacked' restraint file. @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). Cheers, Robbie From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Eleanor Dodson Sent: Wednesday, July 11, 2012 12:15 To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Well - the problem may well be here - in the REFMAC dictionary (see $CLIBD/monomers.s.SO4.cif ) the chiral volume calculation uses at the order of the O numbering around the S atom . So if your O numbering is not right handed you will have the chiral volume calculated as positive, not negative. There are various fixes. Edit the SO4 and just the numbering of 2 of the O atoms - eg use labels: S O2 O1 O3 Or edit the SO4.cif to have SO4 chir_01 S O1 O2 O3 both Eleanor loop_ _chem_comp_chir.comp_id _chem_comp_chir.id _chem_comp_chir.atom_id_centre _chem_comp_chir.atom_id_1 _chem_comp_chir.atom_id_2 _chem_comp_chir.atom_id_3 _chem_comp_chir.volume_sign SO4 chir_01 S O1 O2 O3negativ On 11 July 2012 10:59, Tim Gruene t...@shelx.uni-ac.gwdg.de wrote: -BEGIN PGP SIGNED MESSAGE- Hash: SHA1 Dear Joel, out of curiosity: what is the Chiral volume outliers issue? Cheers, Tim On 07/11/12 01:00, Joel Tyndall wrote: Hi people, We are refining a structure with sulfates and we are getting the Chiral volume outliers issue. I understand the problem as being computational where the oxygens are in reality equivalent but computationally named differently. I have seen the recent Acta Cryst D paper (April 2012 - PDB_REDO) which talks about this issue and mentions the development of Chiron which could fix this issue. Is there a way to fix this problem using existing tools (or editing). We have ~20 sulfates in our protein (10-mer system) Thanks heaps Joel _ Joel Tyndall, PhD Senior Lecturer in Medicinal Chemistry National School of Pharmacy University of Otago PO Box 56 Dunedin 9054 New Zealand Skype: jtyndall Ph: +64 3 479 7293 tel:%2B64%203%20479%207293 - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP/U5+UxlJ7aRr7hoRAqaUAKD4Eo2tqarIwbK6+mHIfYYHcyhAKQCgy02F XK8ZYLNW3gI873nrtkZSv9E= =ishS -END PGP SIGNATURE-
Re: [ccp4bb] Chiral volume outliers SO4
-BEGIN PGP SIGNED MESSAGE- Hash: SHA1 In ccp4-6.3.0, the chiral volume of SO4 is marked as 'both'. SO4 chir_01 S O1 O2 O3both Tim On 07/11/12 12:39, Robbie Joosten wrote: Hi Joel, I prefer the swapping of atom names, which is pretty much what the program chiron does, over hacking the restraint file. The latter makes the problem reappear as soon as you use your PDB file on a machine with an 'unhacked' restraint file. @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). Cheers, Robbie From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Eleanor Dodson Sent: Wednesday, July 11, 2012 12:15 To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Chiral volume outliers SO4 Well - the problem may well be here - in the REFMAC dictionary (see $CLIBD/monomers.s.SO4.cif ) the chiral volume calculation uses at the order of the O numbering around the S atom . So if your O numbering is not right handed you will have the chiral volume calculated as positive, not negative. There are various fixes. Edit the SO4 and just the numbering of 2 of the O atoms - eg use labels: S O2 O1 O3 Or edit the SO4.cif to have SO4 chir_01 S O1 O2 O3 both Eleanor loop_ _chem_comp_chir.comp_id _chem_comp_chir.id _chem_comp_chir.atom_id_centre _chem_comp_chir.atom_id_1 _chem_comp_chir.atom_id_2 _chem_comp_chir.atom_id_3 _chem_comp_chir.volume_sign SO4 chir_01 S O1 O2 O3negativ On 11 July 2012 10:59, Tim Gruene t...@shelx.uni-ac.gwdg.de wrote: Dear Joel, out of curiosity: what is the Chiral volume outliers issue? Cheers, Tim On 07/11/12 01:00, Joel Tyndall wrote: Hi people, We are refining a structure with sulfates and we are getting the Chiral volume outliers issue. I understand the problem as being computational where the oxygens are in reality equivalent but computationally named differently. I have seen the recent Acta Cryst D paper (April 2012 - PDB_REDO) which talks about this issue and mentions the development of Chiron which could fix this issue. Is there a way to fix this problem using existing tools (or editing). We have ~20 sulfates in our protein (10-mer system) Thanks heaps Joel _ Joel Tyndall, PhD Senior Lecturer in Medicinal Chemistry National School of Pharmacy University of Otago PO Box 56 Dunedin 9054 New Zealand Skype: jtyndall Ph: +64 3 479 7293 tel:%2B64%203%20479%207293 - -- - -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A -BEGIN PGP SIGNATURE- Version: GnuPG v1.4.12 (GNU/Linux) Comment: Using GnuPG with Mozilla - http://enigmail.mozdev.org/ iD8DBQFP/Vt+UxlJ7aRr7hoRAu3aAJ9lBBav5Fz9W310QZCA+8hBrvYyEACfe/wV a56yOVyYtgOODEN2ypSLMA0= =9yvs -END PGP SIGNATURE-
Re: [ccp4bb] Chiral volume outliers SO4
On 11 July 2012 11:39, Robbie Joosten robbie_joos...@hotmail.com wrote: @Ian: You’d be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). But this is only because the 'negative' volume sign was erroneously used in the chiral restraint instead of 'both' (or better still IMO no chiral restraint at all), right? If so I don't find it surprising at all that Refmac tried to flip the sulphate and ended up flattening it. Seems to be a good illustration of the GIGO (garbage in - garbage out) principle. Just because the garbage input in this case is in the official CCP4 distribution and not (as is of course more commonly the case) perpetrated by the user doesn't make it any less garbage. The point I was making is that in this and similar cases you don't need a chiral restraint at all: surely 4 bond lengths and 6 bond angles define the chiral volume pretty well already? Or are there cases where without a chiral restraint the refinement still tries to flip the chirality (I would fine that hard to believe). Seems to be a case of belt and braces! Cheers -- Ian
Re: [ccp4bb] Chiral volume outliers SO4
Hi Ian, @Ian: You'd be surprised how well Refmac can flatten sulfates if you have a chiral volume outlier (see Figure 1d in Acta Cryst. D68: 484-496 (2012)). But this is only because the 'negative' volume sign was erroneously used in the chiral restraint instead of 'both' (or better still IMO no chiral restraint at all), right? If so I don't find it surprising at all that Refmac tried to flip the sulphate and ended up flattening it. Seems to be a good illustration of the GIGO (garbage in - garbage out) principle. Just because the garbage input in this case is in the official CCP4 distribution and not (as is of course more commonly the case) perpetrated by the user doesn't make it any less garbage. The problem is that in the creation of chiral volume targets chemically equivalent (groups of) atoms are not recognized as such. So any new or recreated restraint files will have either 'positiv' or 'negativ' and the problem starts all over again. That is why it is better to stay consistent and choose one chirality (the same one as in the 'ideal' coordinates in the PDB ligand descriptions). This will also make it easier compare ligands after aligning them (this applies to ligands more complex than sulfate). Obviously, users should not be forced to deal with these things. Programs like Refmac and COOT should fix chiral volume inversions for the user, because it is only relevant inside the computer. That is the idea of chiron, just fix these 'problems' automatically by swapping equivalent atoms whenever Refmac gives a chiral volume inversion warning. It should make life a bit easier. The point I was making is that in this and similar cases you don't need a chiral restraint at all: surely 4 bond lengths and 6 bond angles define the chiral volume pretty well already? Or are there cases where without a chiral restraint the refinement still tries to flip the chirality (I would fine that hard to believe). I agree with you for sulfate, and also for phosphate ;). I don't know what happens in other compounds at poor resolution, when bond and angle targets (and their SDs) are not equivalent. I guess that some angle might 'give way' before others. That is something that should be tested. I have a growing list of chiral centers that have this problem if you are interested. Cheers, Robbie
[ccp4bb] Chiral volume outliers SO4
Hi people, We are refining a structure with sulfates and we are getting the Chiral volume outliers issue. I understand the problem as being computational where the oxygens are in reality equivalent but computationally named differently. I have seen the recent Acta Cryst D paper (April 2012 - PDB_REDO) which talks about this issue and mentions the development of Chiron which could fix this issue. Is there a way to fix this problem using existing tools (or editing). We have ~20 sulfates in our protein (10-mer system) Thanks heaps Joel _ Joel Tyndall, PhD Senior Lecturer in Medicinal Chemistry National School of Pharmacy University of Otago PO Box 56 Dunedin 9054 New Zealand Skype: jtyndall Ph: +64 3 479 7293
