Re: [ccp4bb] unusual bond lengths in PRODRG cif file
On Mon, 9 Jan 2012, Soisson, Stephen M wrote: I will second Ian's recommendation for GRADE from the Global Phasing group. GRADE overcomes nearly all of the shortcomings we have encountered with other approaches for ligand dictionary generation. Steve, Thanks to you and to Ian Tickle for the positive comments about grade. We have just launched the Grade Web Server so it should be now be much easier for academic and occasional users to generate ligand restraints with it. http://grade.globalphasing.org Regards, Oliver | Dr Oliver Smart | | Global Phasing Ltd., Cambridge UK | | http://www.globalphasing.com/people/osmart/ |
Re: [ccp4bb] unusual bond lengths in PRODRG cif file (Grade Web Server)
On Tue, 10 Jan 2012, Stephen Graham wrote: On 10 January 2012 09:50, John Liebeschuetz wrote: "...available to anyone who has access to the Cambridge Structural Database System" How many academic labs will bother / can afford to buy a CCSD license just to check the geometry of small molecule ligands, especially when they need to do so them only once every blue moon? The ability for the PDB to check a ligand against the CCSD upon deposition would be great. The ability to generate the restraint definition for free via the web before deposition is better: that's why people use PRODRG! Stephen Stephen, We had anticipated your request and got permission from the CCDC to provide a public Web server that would include the use of MOGUL in its invocation of Grade. The Grade Web Server has been publicly launched today, so for ligand restraint definitions that are (partly) based on CSD small molecule structures try using: http://grade.globalphasing.org Regards, Oliver | Dr Oliver Smart | | Global Phasing Ltd., Cambridge UK | | http://www.globalphasing.com/people/osmart/ |
Re: [ccp4bb] unusual bond lengths in PRODRG cif file (Another possibility - direct use of QM)
On Mon, 9 Jan 2012, krish wrote: You can use Phenix.elbow or phenix.reel to load the coordinates of the small moleucle and optimize with AM1 (semi-empirical), then you should get reasonable geometirc parameters suc as bond length, bond angles and etc. Hope this helps ! Cheers, Krishna Krishna Chinthalapudi, PhD Hannover Medical School Shveta and Krishna, Just to point out that an alternative to using QM methods as a source of ligand restraints for refinement is to directly use the methods to represent the ligand chemistry during refinement. BUSTER provides the facility to do this see: http://www.globalphasing.com/buster/wiki/index.cgi?AutobusterLigandQMIntroduction It is pretty easy to do, particularly for semi-empirical QM methods (such as AM1 or the superior RM1). An advantage is that instead of coming up with approximate restraints sourced from AM1 then the actual method itself is used. Regards, Oliver | Dr Oliver Smart | | Global Phasing Ltd., Cambridge UK | | http://www.globalphasing.com/people/osmart/ |
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
Hi Guys, I just want to make aware that apart form PRODRG etc there exist also PURY server http://pury.ijs.si/, which offers a possibility to create restraints for heteromolecules. It accepts PDB files, smiles format. Alternatively JME editor can be used to draw your compound. PURY: a database of geometric restraints of hetero compounds for refinement in complexes with macromolecular structures Miha Andrejasˇicˇ, Jure Prazˇnikar and Dusˇan Turk Acta Cryst. (2008). D64, 1093–1109) Its parameters are extracted from CSD. Its unlimited use is restrained to the CSD license holders, whereas for a small number of downloads its use is not restrained. dusan Dr. Dusan Turk, Assoc. Prof. Head of Structural Biology Group Head of Centre for Protein and Structure Production Centre of excellence for Integrated Approaches in Chemistry and Biology of Proteins, Scientific Director Professor of Structural Biology at IPS "Jozef Stefan" e-mail: dusan.t...@ijs.sihttp://bio.ijs.si/sbl/ phone: +386 1 477 3857 Dept. of Biochem.& Mol.& Struct. Biol. fax: +386 1 477 3984 Jozef Stefan Institute Jamova 39, 1 000 Ljubljana,Slovenia Skype: dusan.turk (voice over internet: www.skype.com
Re: [ccp4bb] : Re: [ccp4bb] unusual bond lengths in PRODRG cif file
Dear Stephen, The thought that using the CSD via Mogul for generating good refinement dictionaries in the first place was THE way to go, rather than relying on the PDB to use the same information later to try and catch errors at the time of deposition, has been the driving force in the development of Grade by Oliver Smart and Thomas Womack at Global Phasing, thanks to a very fruitful interaction with the CCDC. Grade generates restraints using Mogul for data mining CSD structures. Where this data mining does not provide sufficient information, quantum chemical methods are used. Grade produces restraints not only on bond lengths and bond angles, but also on planarity and on torsion angles. To get the best restraints, access to Mogul is required; but if you do not have access to it, you can run it via the command "grade -nomogul". More information can be found on the following page of the BUSTER Wiki: http://www.globalphasing.com/buster/wiki/index.cgi?BusterLigandRestraints and, through the "grade" hyperlink on that page or directly, at http://www.globalphasing.com/buster/wiki/index.cgi?GradeMainPage Oliver Smart covered Grade in his talk at last year's CCP4 Study Weekend. Grade was released to our beta users on 8 October 2010 and to academics as part of the BUSTER release on 20 July 2011. The latter is available free of charge via the BUSTER homepage at http://www.globalphasing.com/buster/ Any users whom Colin Groom would enable to connect to their nearest CSD installation would immediately be able to use Grade's full capabilities. I would recommend that anyone seriously interested in ligand stereochemistry should take up Colin's offer. I should add that, with the kind and gratefully acknowledged permission of the CCDC, we are currently working on a Web server version of Grade for use by academics. With best wishes, Gerard. -- On Tue, Jan 10, 2012 at 10:23:02AM +, Stephen Graham wrote: > "...available to anyone who has access to the Cambridge Structural > Database System" > > How many academic labs will bother / can afford to buy a CCSD license > just to check the geometry of small molecule ligands, especially when > they need to do so them only once every blue moon? > > The ability for the PDB to check a ligand against the CCSD upon > deposition would be great. The ability to generate the restraint > definition for free via the web before deposition is better: that's > why people use PRODRG! > > Stephen > > On 10 January 2012 09:50, John Liebeschuetz wrote: > > On 9 January 2012 06:13, Shveta Bisht wrote: > >> Dear all > >> > >> I have generated a refmac cif file for a molecule using PRODRG. I used > >> JME editor to draw the molecule and ran PRODRG online with the > >> options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the > >> attachments for the molecule drawing and the expected bond lengths as > >> listed in the PRODRG generated cif file. There are some unusual > >> values. I have listed them below along with the likely explanations > >> (just guesses). > >> > >> DRG CAR CAK single 1.390 0.025 DRG CAQ > >> CAB single 1.390 0.025 DRG CAT CAI single > >> 1.390 0.020 All three are C-C single bonds where one of the carbons > >> belong to aromatic ring. This might lead to a short bond, although > >> 1.39 seems to be too short for this. > >> > >> DRG CAI NAL double 1.340 0.022 DRG CAP > >> NAL single 1.340 0.022 Here N and both the carbons are > >> sp2 hybridization, so there can be delocalization of electrons. Thus > >> both bonds (single and double) are of similar length. > >> > >> DRG CAP CAA double 1.530 0.025 As mentioned > >> above, if pi (unhybridized) electrons of CAP are involved in CAP NAL > >> bonding, then CAP CAA double bond essentially becomes a single bond > >> with 1.53 bond length. > >> > >> I need advise on the way I have run prodrg and the explanations for the > >> results. > >> Is it common to observe such values? Or it is due to the alternating > >> single and double bonds in this structure. > > > > Dear Shveta, > > > > I'd like to follow up Ian Tickle's answer. A survey we carried out > > recently suggested that up to 70% of ligand structures in the PDB had bond > > and bond angle errors that could have been removed by better choice of > > restraints (to be published). Although most of the errors found are small, > > some were very large (> 10 s.d. from mean). > > > > The Mogul program (http://www.ccdc.cam.ac.uk/products/csd_system/mogul/) > > can be used to analyse the geometry of any feature in a 3D ligand model > > against data in the Cambridge Structural Database and is available to > > anyone who has access to the Cambridge Structural Database System. The > > GRADE dictionary generation software from Global Phasing uses Mogul > > informa
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
Thanks Colin! I was also going to mention the Chemical Database Service, available to UK academics. Their website is http://cds.dl.ac.uk/ In fact, the very nice and friendly CDS guys are just across the corridor from me, so please let me know if you have problems/questions. Cheers Martyn On Tue, 2012-01-10 at 12:53 +, Colin Groom wrote: > I'm sad to think that scientists may not 'bother' to use the CSD > system 'just' to check the geometry of small molecule ligands, as they > may, of course, be the main focus of the study, or the focus of > subsequent researchers who use the structures. Moreover, comparison of > small molecule and protein-bound ligand structures can be most > revealing. > > In answer to your question of access, the vast majority of research > universities in the world (with a chemistry department) already have > access to the CSD. In fact it is available in 72 counties, to > scientists in around 1,500 institutions. The problem you highlight is > that it's quite common for scientists not to realise that another > department, or their institutions library, already provide access to > the CSD system. I'll reply to any off-board emails should folks want > to know who their local contact is. > > In terms of affordability, the CSD system is maintained by the > Cambridge Crystallographic Data Centre, which is a non-profit, > charitable organisation. It is available at below cost to academics. > Anyone who genuinely cannot afford the modest charge, which is used > for the ongoing funding of the CSD, is of course given free access. > The CSD and other chemistry databases are also freely available to UK > researchers through the excellent (EPSRC funded) Chemical Database > Service operated from Daresbury. > > You're right that the CCDC:PDB collaboration to develop on-line tools > check ligands and generate dictionaries 'is great'- and Gerard might > let us know how he's getting on? > > Colin > > Dr Colin R Groom > Email: gr...@ccdc.cam.ac.uk > Executive Director > Phone-direct: +44-(0)1223-336020 > Cambridge Crystallographic Data Centre > Phone-messages: +44-(0)1223-336408 > 12 Union > Road FAX:+44-(0)1223-336033 > Cambridge CB2 1EZ, UK Website: > http://www.ccdc.cam.ac.uk > > > > > > -Original Message- > From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Stephen > Graham > Sent: 10 January 2012 10:23 > To: CCP4BB@JISCMAIL.AC.UK > Subject: Re: [ccp4bb] : Re: [ccp4bb] unusual bond lengths in PRODRG cif file > > "...available to anyone who has access to the Cambridge Structural > Database System" > > How many academic labs will bother / can afford to buy a CCSD license > just to check the geometry of small molecule ligands, especially when > they need to do so them only once every blue moon? > > The ability for the PDB to check a ligand against the CCSD upon > deposition would be great. The ability to generate the restraint > definition for free via the web before deposition is better: that's > why people use PRODRG! > > Stephen > > On 10 January 2012 09:50, John Liebeschuetz wrote: > > On 9 January 2012 06:13, Shveta Bisht wrote: > >> Dear all > >> > >> I have generated a refmac cif file for a molecule using PRODRG. I used > >> JME editor to draw the molecule and ran PRODRG online with the > >> options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the > >> attachments for the molecule drawing and the expected bond lengths as > >> listed in the PRODRG generated cif file. There are some unusual > >> values. I have listed them below along with the likely explanations > >> (just guesses). > >> > >> DRG CARCAK single 1.3900.025 DRG CAQ > >> CAB single 1.3900.025 DRG CATCAI single > >> 1.3900.020 All three are C-C single bonds where one of the carbons > >> belong to aromatic ring. This might lead to a short bond, although > >> 1.39 seems to be too short for this. > >> > >> DRG CAINAL double 1.3400.022 DRG CAP > >> NAL single 1.3400.022 Here N and both the carbons are > >> sp2 hybridization, so there can be delocalization of electrons. Thus > >> both bonds (single and double) are of similar length. > >> > >> DRG CAPCAA double 1.5300.025 As mentioned > >> above, if pi (unhybridized) electrons of CAP are involved in CAP NAL > >> bonding, then CAP CAA do
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
I'm sad to think that scientists may not 'bother' to use the CSD system 'just' to check the geometry of small molecule ligands, as they may, of course, be the main focus of the study, or the focus of subsequent researchers who use the structures. Moreover, comparison of small molecule and protein-bound ligand structures can be most revealing. In answer to your question of access, the vast majority of research universities in the world (with a chemistry department) already have access to the CSD. In fact it is available in 72 counties, to scientists in around 1,500 institutions. The problem you highlight is that it's quite common for scientists not to realise that another department, or their institutions library, already provide access to the CSD system. I'll reply to any off-board emails should folks want to know who their local contact is. In terms of affordability, the CSD system is maintained by the Cambridge Crystallographic Data Centre, which is a non-profit, charitable organisation. It is available at below cost to academics. Anyone who genuinely cannot afford the modest charge, which is used for the ongoing funding of the CSD, is of course given free access. The CSD and other chemistry databases are also freely available to UK researchers through the excellent (EPSRC funded) Chemical Database Service operated from Daresbury. You're right that the CCDC:PDB collaboration to develop on-line tools check ligands and generate dictionaries 'is great'- and Gerard might let us know how he's getting on? Colin Dr Colin R Groom Email: gr...@ccdc.cam.ac.uk Executive Director Phone-direct: +44-(0)1223-336020 Cambridge Crystallographic Data Centre Phone-messages: +44-(0)1223-336408 12 Union Road FAX:+44-(0)1223-336033 Cambridge CB2 1EZ, UK Website: http://www.ccdc.cam.ac.uk -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Stephen Graham Sent: 10 January 2012 10:23 To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] : Re: [ccp4bb] unusual bond lengths in PRODRG cif file "...available to anyone who has access to the Cambridge Structural Database System" How many academic labs will bother / can afford to buy a CCSD license just to check the geometry of small molecule ligands, especially when they need to do so them only once every blue moon? The ability for the PDB to check a ligand against the CCSD upon deposition would be great. The ability to generate the restraint definition for free via the web before deposition is better: that's why people use PRODRG! Stephen On 10 January 2012 09:50, John Liebeschuetz wrote: > On 9 January 2012 06:13, Shveta Bisht wrote: >> Dear all >> >> I have generated a refmac cif file for a molecule using PRODRG. I used >> JME editor to draw the molecule and ran PRODRG online with the >> options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the >> attachments for the molecule drawing and the expected bond lengths as >> listed in the PRODRG generated cif file. There are some unusual >> values. I have listed them below along with the likely explanations >> (just guesses). >> >> DRG CAR CAK single 1.390 0.025 DRG CAQ >> CAB single 1.390 0.025 DRG CAT CAI single >> 1.390 0.020 All three are C-C single bonds where one of the carbons >> belong to aromatic ring. This might lead to a short bond, although >> 1.39 seems to be too short for this. >> >> DRG CAI NAL double 1.340 0.022 DRG CAP >> NAL single 1.340 0.022 Here N and both the carbons are >> sp2 hybridization, so there can be delocalization of electrons. Thus >> both bonds (single and double) are of similar length. >> >> DRG CAP CAA double 1.530 0.025 As mentioned >> above, if pi (unhybridized) electrons of CAP are involved in CAP NAL >> bonding, then CAP CAA double bond essentially becomes a single bond >> with 1.53 bond length. >> >> I need advise on the way I have run prodrg and the explanations for the >> results. >> Is it common to observe such values? Or it is due to the alternating >> single and double bonds in this structure. > > Dear Shveta, > > I'd like to follow up Ian Tickle's answer. A survey we carried out recently > suggested that up to 70% of ligand structures in the PDB had bond and bond > angle errors that could have been removed by better choice of restraints (to > be published). Although most of the errors found are small, some were very > large (> 10 s.d. from mean). > > The
Re: [ccp4bb] : Re: [ccp4bb] unusual bond lengths in PRODRG cif file
"...available to anyone who has access to the Cambridge Structural Database System" How many academic labs will bother / can afford to buy a CCSD license just to check the geometry of small molecule ligands, especially when they need to do so them only once every blue moon? The ability for the PDB to check a ligand against the CCSD upon deposition would be great. The ability to generate the restraint definition for free via the web before deposition is better: that's why people use PRODRG! Stephen On 10 January 2012 09:50, John Liebeschuetz wrote: > On 9 January 2012 06:13, Shveta Bisht wrote: >> Dear all >> >> I have generated a refmac cif file for a molecule using PRODRG. I used >> JME editor to draw the molecule and ran PRODRG online with the >> options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the >> attachments for the molecule drawing and the expected bond lengths as >> listed in the PRODRG generated cif file. There are some unusual >> values. I have listed them below along with the likely explanations >> (just guesses). >> >> DRG CAR CAK single 1.390 0.025 DRG CAQ >> CAB single 1.390 0.025 DRG CAT CAI single >> 1.390 0.020 All three are C-C single bonds where one of the carbons >> belong to aromatic ring. This might lead to a short bond, although >> 1.39 seems to be too short for this. >> >> DRG CAI NAL double 1.340 0.022 DRG CAP >> NAL single 1.340 0.022 Here N and both the carbons are >> sp2 hybridization, so there can be delocalization of electrons. Thus >> both bonds (single and double) are of similar length. >> >> DRG CAP CAA double 1.530 0.025 As mentioned >> above, if pi (unhybridized) electrons of CAP are involved in CAP NAL >> bonding, then CAP CAA double bond essentially becomes a single bond >> with 1.53 bond length. >> >> I need advise on the way I have run prodrg and the explanations for the >> results. >> Is it common to observe such values? Or it is due to the alternating >> single and double bonds in this structure. > > Dear Shveta, > > I'd like to follow up Ian Tickle's answer. A survey we carried out recently > suggested that up to 70% of ligand structures in the PDB had bond and bond > angle errors that could have been removed by better choice of restraints (to > be published). Although most of the errors found are small, some were very > large (> 10 s.d. from mean). > > The Mogul program (http://www.ccdc.cam.ac.uk/products/csd_system/mogul/) can > be used to analyse the geometry of any feature in a 3D ligand model against > data in the Cambridge Structural Database and is available to anyone who has > access to the Cambridge Structural Database System. The GRADE dictionary > generation software from Global Phasing uses Mogul information behind the > scenes to generate bond and bond angle restraints. In addition ligand > validation and restraint correction using Mogul will become available via > COOT before too long. Finally you might like to know we are working with the > PDB so that the geometry of ligand models can be validated on submission. > > Regards > John > > Dr John W. Liebeschuetz > Research & Applications Manager > Cambridge Crystallographic Data Centre > 12 Union Rd., Cambridge CB2 1EZ, UK > T: +44-(0)1223-762532 > F: +44-(0)1223-336033 > > > > LEGAL NOTICE > Unless expressly stated otherwise, information contained in this > message is confidential. If this message is not intended for you, > please inform postmas...@ccdc.cam.ac.uk and delete the message. > The Cambridge Crystallographic Data Centre is a company Limited > by Guarantee and a Registered Charity. > Registered in England No. 2155347 Registered Charity No. 800579 > Registered office 12 Union Road, Cambridge CB2 1EZ. -- Dr Stephen Graham 1851 Research Fellow Cambridge Institute for Medical Research Wellcome Trust/MRC Building Addenbrooke's Hospital, Hills Road Cambridge, CB2 0XY, UK Phone: +44 1223 762 638
[ccp4bb] : Re: [ccp4bb] unusual bond lengths in PRODRG cif file
On 9 January 2012 06:13, Shveta Bisht wrote: > Dear all > > I have generated a refmac cif file for a molecule using PRODRG. I used > JME editor to draw the molecule and ran PRODRG online with the > options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the > attachments for the molecule drawing and the expected bond lengths as > listed in the PRODRG generated cif file. There are some unusual > values. I have listed them below along with the likely explanations > (just guesses). > > DRG CARCAK single 1.3900.025 DRG CAQ > CAB single 1.3900.025 DRG CATCAI single > 1.3900.020 All three are C-C single bonds where one of the carbons > belong to aromatic ring. This might lead to a short bond, although > 1.39 seems to be too short for this. > > DRG CAINAL double 1.3400.022 DRG CAP > NAL single 1.3400.022 Here N and both the carbons are > sp2 hybridization, so there can be delocalization of electrons. Thus > both bonds (single and double) are of similar length. > > DRG CAPCAA double 1.5300.025 As mentioned > above, if pi (unhybridized) electrons of CAP are involved in CAP NAL > bonding, then CAP CAA double bond essentially becomes a single bond > with 1.53 bond length. > > I need advise on the way I have run prodrg and the explanations for the > results. > Is it common to observe such values? Or it is due to the alternating > single and double bonds in this structure. Dear Shveta, I'd like to follow up Ian Tickle's answer. A survey we carried out recently suggested that up to 70% of ligand structures in the PDB had bond and bond angle errors that could have been removed by better choice of restraints (to be published). Although most of the errors found are small, some were very large (> 10 s.d. from mean). The Mogul program (http://www.ccdc.cam.ac.uk/products/csd_system/mogul/) can be used to analyse the geometry of any feature in a 3D ligand model against data in the Cambridge Structural Database and is available to anyone who has access to the Cambridge Structural Database System. The GRADE dictionary generation software from Global Phasing uses Mogul information behind the scenes to generate bond and bond angle restraints. In addition ligand validation and restraint correction using Mogul will become available via COOT before too long. Finally you might like to know we are working with the PDB so that the geometry of ligand models can be validated on submission. Regards John Dr John W. Liebeschuetz Research & Applications Manager Cambridge Crystallographic Data Centre 12 Union Rd., Cambridge CB2 1EZ, UK T: +44-(0)1223-762532 F: +44-(0)1223-336033 LEGAL NOTICE Unless expressly stated otherwise, information contained in this message is confidential. If this message is not intended for you, please inform postmas...@ccdc.cam.ac.uk and delete the message. The Cambridge Crystallographic Data Centre is a company Limited by Guarantee and a Registered Charity. Registered in England No. 2155347 Registered Charity No. 800579 Registered office 12 Union Road, Cambridge CB2 1EZ.
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
To elaborate further on software packages available that do a reasonable job of fitting small molecules and outputting reasonable dictionaries, one could consider Afitt from OpenEye Scientific Software. They have academic as well as commercial licenses to their software. Cheers, tom -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Ian Tickle Sent: Monday, 9 January 2012 11:40 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] unusual bond lengths in PRODRG cif file On 9 January 2012 06:13, Shveta Bisht wrote: > Dear all > > I have generated a refmac cif file for a molecule using PRODRG. I used > JME editor to draw the molecule and ran PRODRG online with the > options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the > attachments for the molecule drawing and the expected bond lengths as > listed in the PRODRG generated cif file. There are some unusual > values. I have listed them below along with the likely explanations > (just guesses). > > DRG CAR CAK single 1.390 0.025 > DRG CAQ CAB single 1.390 0.025 > DRG CAT CAI single 1.390 0.020 > All three are C-C single bonds where one of the carbons belong to > aromatic ring. This might lead to a short bond, although 1.39 seems to > be too short for this. > > DRG CAI NAL double 1.340 0.022 > DRG CAP NAL single 1.340 0.022 > Here N and both the carbons are sp2 hybridization, so there can be > delocalization of electrons. Thus both bonds (single and double) are > of similar length. > > DRG CAP CAA double 1.530 0.025 > As mentioned above, if pi (unhybridized) electrons of CAP are involved > in CAP NAL bonding, then CAP CAA double bond essentially becomes a > single bond with 1.53 bond length. > > I need advise on the way I have run prodrg and the explanations for the > results. > Is it common to observe such values? Or it is due to the alternating single > and > double bonds in this structure. Dear Shveta I agree completely with your assessment, there are certainly some "unusual" values, but I think this goes beyond "mistakes". I have run your structure through our own dictionary auto-generation software which essentially takes suitable fragments from the CSD and stitches them together (similar to CCDC-MOGUL but it doesn't use MOGUL and the pieces are smaller). Here are the values I get for comparison: > DRG CARCAK single 1.3900.025 1.512(10) > DRG CAQCAB single 1.3900.025 1.498(7) > DRG CATCAIsingle 1.3900.020 1.449(24) > DRG CAI NAL double 1.3400.022 1.273(13) > DRG CAPNAL single 1.3400.022 1.350(28) > DRG CAPCAA double1.5300.025 1.329(21) so essentially backing up what you said. My suspicion is that it's not generally recognised the central role played by bond length & angle restraints in MX refinement (after all if they weren't important then we wouldn't need to use them!), and as a consequence some people seem to think that their exact values are unimportant and "anything will do". Their importance soon becomes obvious (particularly of course at medium-low resolution) if you try to do unrestrained refinement: then you can easily get deviations 10 times greater than you get with restraints. So personally I believe in using the most accurate restraints possible and "anything will NOT do". My main concern would be that grossly inaccurate values such as these find their way into the PDB and then people base their restraints on these structures (though it's not a great idea to use the PDB co-ordinates as a source of restraints!). Before you ask, unfortunately our software is not available for distribution but I can recommend GRADE from Global Phasing which gives very high quality restraints; there's also of course JLigand from CCP4, though I haven't used it personally and so cannot attest for the quality. Cheers -- Ian
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
I will second Ian's recommendation for GRADE from the Global Phasing group. GRADE overcomes nearly all of the shortcomings we have encountered with other approaches for ligand dictionary generation. Best- Steve -Original Message- From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Ian Tickle Sent: Monday, January 09, 2012 7:40 AM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] unusual bond lengths in PRODRG cif file On 9 January 2012 06:13, Shveta Bisht wrote: > Dear all > > I have generated a refmac cif file for a molecule using PRODRG. I used > JME editor to draw the molecule and ran PRODRG online with the > options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the > attachments for the molecule drawing and the expected bond lengths as > listed in the PRODRG generated cif file. There are some unusual > values. I have listed them below along with the likely explanations > (just guesses). > > DRG CAR CAK single 1.390 0.025 > DRG CAQ CAB single 1.390 0.025 > DRG CAT CAI single 1.390 0.020 > All three are C-C single bonds where one of the carbons belong to > aromatic ring. This might lead to a short bond, although 1.39 seems to > be too short for this. > > DRG CAI NAL double 1.340 0.022 > DRG CAP NAL single 1.340 0.022 > Here N and both the carbons are sp2 hybridization, so there can be > delocalization of electrons. Thus both bonds (single and double) are > of similar length. > > DRG CAP CAA double 1.530 0.025 > As mentioned above, if pi (unhybridized) electrons of CAP are involved > in CAP NAL bonding, then CAP CAA double bond essentially becomes a > single bond with 1.53 bond length. > > I need advise on the way I have run prodrg and the explanations for the > results. > Is it common to observe such values? Or it is due to the alternating single > and > double bonds in this structure. Dear Shveta I agree completely with your assessment, there are certainly some "unusual" values, but I think this goes beyond "mistakes". I have run your structure through our own dictionary auto-generation software which essentially takes suitable fragments from the CSD and stitches them together (similar to CCDC-MOGUL but it doesn't use MOGUL and the pieces are smaller). Here are the values I get for comparison: > DRG CARCAK single 1.3900.025 1.512(10) > DRG CAQCAB single 1.3900.025 1.498(7) > DRG CATCAIsingle 1.3900.020 1.449(24) > DRG CAI NAL double 1.3400.022 1.273(13) > DRG CAPNAL single 1.3400.022 1.350(28) > DRG CAPCAA double1.5300.025 1.329(21) so essentially backing up what you said. My suspicion is that it's not generally recognised the central role played by bond length & angle restraints in MX refinement (after all if they weren't important then we wouldn't need to use them!), and as a consequence some people seem to think that their exact values are unimportant and "anything will do". Their importance soon becomes obvious (particularly of course at medium-low resolution) if you try to do unrestrained refinement: then you can easily get deviations 10 times greater than you get with restraints. So personally I believe in using the most accurate restraints possible and "anything will NOT do". My main concern would be that grossly inaccurate values such as these find their way into the PDB and then people base their restraints on these structures (though it's not a great idea to use the PDB co-ordinates as a source of restraints!). Before you ask, unfortunately our software is not available for distribution but I can recommend GRADE from Global Phasing which gives very high quality restraints; there's also of course JLigand from CCP4, though I haven't used it personally and so cannot attest for the quality. Cheers -- Ian Notice: This e-mail message, together with any attachments, contains information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New Jersey, USA 08889), and/or its affiliates Direct contact information for affiliates is available at http://www.merck.com/contact/contacts.html) that may be confidential, proprietary copyrighted and/or legally privileged. It is intended solely for the use of the individual or entity named on this message. If you are not the intended recipient, and have received this message in error, please notify us immediately by reply e-mail and then delete it from your system.
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
On 9 January 2012 06:13, Shveta Bisht wrote: > Dear all > > I have generated a refmac cif file for a molecule using PRODRG. I used > JME editor to draw the molecule and ran PRODRG online with the > options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the > attachments for the molecule drawing and the expected bond lengths as > listed in the PRODRG generated cif file. There are some unusual > values. I have listed them below along with the likely explanations > (just guesses). > > DRG CAR CAK single 1.390 0.025 > DRG CAQ CAB single 1.390 0.025 > DRG CAT CAI single 1.390 0.020 > All three are C-C single bonds where one of the carbons belong to > aromatic ring. This might lead to a short bond, although 1.39 seems to > be too short for this. > > DRG CAI NAL double 1.340 0.022 > DRG CAP NAL single 1.340 0.022 > Here N and both the carbons are sp2 hybridization, so there can be > delocalization of electrons. Thus both bonds (single and double) are > of similar length. > > DRG CAP CAA double 1.530 0.025 > As mentioned above, if pi (unhybridized) electrons of CAP are involved > in CAP NAL bonding, then CAP CAA double bond essentially becomes a > single bond with 1.53 bond length. > > I need advise on the way I have run prodrg and the explanations for the > results. > Is it common to observe such values? Or it is due to the alternating single > and > double bonds in this structure. Dear Shveta I agree completely with your assessment, there are certainly some "unusual" values, but I think this goes beyond "mistakes". I have run your structure through our own dictionary auto-generation software which essentially takes suitable fragments from the CSD and stitches them together (similar to CCDC-MOGUL but it doesn't use MOGUL and the pieces are smaller). Here are the values I get for comparison: > DRG CARCAK single 1.3900.025 1.512(10) > DRG CAQCAB single 1.3900.025 1.498(7) > DRG CATCAIsingle 1.3900.020 1.449(24) > DRG CAI NAL double 1.3400.022 1.273(13) > DRG CAPNAL single 1.3400.022 1.350(28) > DRG CAPCAA double1.5300.025 1.329(21) so essentially backing up what you said. My suspicion is that it's not generally recognised the central role played by bond length & angle restraints in MX refinement (after all if they weren't important then we wouldn't need to use them!), and as a consequence some people seem to think that their exact values are unimportant and "anything will do". Their importance soon becomes obvious (particularly of course at medium-low resolution) if you try to do unrestrained refinement: then you can easily get deviations 10 times greater than you get with restraints. So personally I believe in using the most accurate restraints possible and "anything will NOT do". My main concern would be that grossly inaccurate values such as these find their way into the PDB and then people base their restraints on these structures (though it's not a great idea to use the PDB co-ordinates as a source of restraints!). Before you ask, unfortunately our software is not available for distribution but I can recommend GRADE from Global Phasing which gives very high quality restraints; there's also of course JLigand from CCP4, though I haven't used it personally and so cannot attest for the quality. Cheers -- Ian
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
Thank you Shveta for NOTICING!!! Please - everyone - check your restraints - programs make mistakes - you (or the chemist who made the ligand) - are the experts Eleanor On 01/09/2012 10:05 AM, krish wrote: Dear Shveta, I have seen similar trends with PRODRG. I recommend you to use other molecular modeling programs like Hyperchem or Maestro to get more consistent geometric parameters for small molecules. Once you know the bondlengths and bond angles from aforesaid molecular modeling programs, you can use sketcher (CCP4) to define them manually. Save it to the monomer library and you are all set to run them in Refmac . or You can use Phenix.elbow or phenix.reel to load the coordinates of the small moleucle and optimize with AM1 (semi-empirical), then you should get reasonable geometirc parameters suc as bond length, bond angles and etc. Hope this helps ! Cheers, Krishna Krishna Chinthalapudi, PhD Hannover Medical School On Mon, Jan 9, 2012 at 7:13 AM, Shveta Bishtwrote: Dear all I have generated a refmac cif file for a molecule using PRODRG. I used JME editor to draw the molecule and ran PRODRG online with the options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the attachments for the molecule drawing and the expected bond lengths as listed in the PRODRG generated cif file. There are some unusual values. I have listed them below along with the likely explanations (just guesses). DRG CARCAK single 1.3900.025 DRG CAQCAB single 1.3900.025 DRG CATCAI single 1.3900.020 All three are C-C single bonds where one of the carbons belong to aromatic ring. This might lead to a short bond, although 1.39 seems to be too short for this. DRG CAINAL double 1.3400.022 DRG CAPNAL single 1.3400.022 Here N and both the carbons are sp2 hybridization, so there can be delocalization of electrons. Thus both bonds (single and double) are of similar length. DRG CAPCAA double 1.5300.025 As mentioned above, if pi (unhybridized) electrons of CAP are involved in CAP NAL bonding, then CAP CAA double bond essentially becomes a single bond with 1.53 bond length. I need advise on the way I have run prodrg and the explanations for the results. Is it common to observe such values? Or it is due to the alternating single and double bonds in this structure. -- Shveta Bisht Ph.D. Student, Prof. M R N Murthy's Group, Molecular Biophysics Unit, Indian Institute of Science Bangalore-12 -- This message has been scanned for viruses and dangerous content by MailScanner, and is believed to be clean.
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
On 09/01/12 06:13, Shveta Bisht wrote: I need advise on the way I have run prodrg and the explanations for the results. There is little room for manoeuvre when running prodrg. Prodrg is not the Font of All Ligand Wisdom. Prodrg makes mistakes. If you think that the bond lengths are wrong, change them. You can use CCDC's Mogul to assist in the restraints manipulation. Is it common to observe such values? Or it is due to the alternating single and double bonds in this structure. You can test this yourself by generating different but related ligands. You might like to use the CCP4 version rather than the web version which it seems that you are currently using. Other restraints-generating software is available. HTH, Paul.
Re: [ccp4bb] unusual bond lengths in PRODRG cif file
Dear Shveta, I have seen similar trends with PRODRG. I recommend you to use other molecular modeling programs like Hyperchem or Maestro to get more consistent geometric parameters for small molecules. Once you know the bondlengths and bond angles from aforesaid molecular modeling programs, you can use sketcher (CCP4) to define them manually. Save it to the monomer library and you are all set to run them in Refmac . or You can use Phenix.elbow or phenix.reel to load the coordinates of the small moleucle and optimize with AM1 (semi-empirical), then you should get reasonable geometirc parameters suc as bond length, bond angles and etc. Hope this helps ! Cheers, Krishna Krishna Chinthalapudi, PhD Hannover Medical School On Mon, Jan 9, 2012 at 7:13 AM, Shveta Bisht wrote: > Dear all > > I have generated a refmac cif file for a molecule using PRODRG. I used > JME editor to draw the molecule and ran PRODRG online with the > options: Chirality-Yes, Charges-Reduced and EM-Yes. Please check the > attachments for the molecule drawing and the expected bond lengths as > listed in the PRODRG generated cif file. There are some unusual > values. I have listed them below along with the likely explanations > (just guesses). > > DRG CARCAK single 1.3900.025 > DRG CAQCAB single 1.3900.025 > DRG CATCAI single 1.3900.020 > All three are C-C single bonds where one of the carbons belong to > aromatic ring. This might lead to a short bond, although 1.39 seems to > be too short for this. > > DRG CAINAL double 1.3400.022 > DRG CAPNAL single 1.3400.022 > Here N and both the carbons are sp2 hybridization, so there can be > delocalization of electrons. Thus both bonds (single and double) are > of similar length. > > DRG CAPCAA double 1.5300.025 > As mentioned above, if pi (unhybridized) electrons of CAP are involved > in CAP NAL bonding, then CAP CAA double bond essentially becomes a > single bond with 1.53 bond length. > > I need advise on the way I have run prodrg and the explanations for the > results. > Is it common to observe such values? Or it is due to the alternating > single and > double bonds in this structure. > > -- > Shveta Bisht > Ph.D. Student, > Prof. M R N Murthy's Group, > Molecular Biophysics Unit, > Indian Institute of Science > Bangalore-12 > -- > This message has been scanned for viruses and > dangerous content by MailScanner, and is > believed to be clean. > >
