From Filippo.Marchioni at cchmc.org Mon Jul 9 08:48:08 2007 From: Filippo.Marchioni at cchmc.org (Filippo Marchioni) Date: Mon, 09 Jul 2007 11:48:08 -0400 Subject: [Zinc-fans] help Message-ID: Dear ZINC users, I am new on this mailing list and I hope my question will be appropriate. I notice that in compounds like ZINC01607240 (3-[4-[(4-amino-1,2-dimethyl-6-quinolyl)amino]-1,6-dimethyl-pyrimidin-2-yl]-1-(4-methoxyphenyl)-guanidine) the pyrimidin and the quinolin group are positively charged but the charge assigned in the mol2 file for these two nitrogen still negative. Am I completely missing the point or there is a problem? Thanks for your help best Filippo From mikesilb at bnl.gov Wed Jul 11 06:26:41 2007 From: mikesilb at bnl.gov (Silberstein, Michael) Date: Wed, 11 Jul 2007 09:26:41 -0400 Subject: [Zinc-fans] Error messages when docking specific molecules within ZINC-derived library Message-ID: Hi, I am a novice at docking larger libraries, and so, the following inquiry represents some of my current difficulties in docking (using DOCK 4.0.1) a ZINC-database derived mini-library. I have attempted to dock a library of ~3000 compounds to various zinc-metalloproteases. Even though 3000 separate molecules were included (in one large .mol2 file), only ~ 600 of them were able to provide docking results. The remaining 2400 compounds gave the following error: WARNING read_mol2: Error reading ATOM record for ZINC00001648 in ./xyz.mol2. WARNING read_mol2: Error reading ATOM record for ZINC00001825 in ./xyz.mol2. WARNING read_mol2: Improper BOND origin/target for ZINC00001932 in ./xyz.mol2. WARNING read_mol2: Error reading ATOM record for ZINC00002585 in ./xyz.mol2. WARNING read_mol2: Error reading ATOM record for ZINC00002588 in ./xyz.mol2. WARNING read_mol2: Error reading ATOM record for ZINC00002819 in ./xyz.mol2. WARNING read_mol2: Improper BOND origin/target for ZINC00003421 in ./xyz.mol2. and so on... Can anyone explain to me what might be wrong with the format of these individual .mol2 files such that either the ATOMs or BONDs cannot be read-in properly in order to have these molecules docked?? Since this analysis has been already performed using DOCK 4.0, it would be really good if I would not have to potentially repeat this using a newer version of DOCK. So it would be preferable if any suggestions/comments be regarding (specifically) DOCK 4.0 and why the program is having trouble reading in such a large percentage of ZINC database-derived .mol2 files. Any suggestion would be very helpful at this point. Thanks in advance. Sincerely, Mike Silberstein From mikesilb at bnl.gov Wed Jul 11 07:16:59 2007 From: mikesilb at bnl.gov (Silberstein, Michael) Date: Wed, 11 Jul 2007 10:16:59 -0400 Subject: [Zinc-fans] Further analysis of the error messages when docking ZINC-derived library Message-ID: Hi again, This post is highly related to the last post that I made "Error messages when docking specific molecules withinZINC-derived library" and has more detail as to my current difficulties. In the last post, I mentioned that many compounds in my ZINC database-derived library had errors of the form WARNING read_mol2: Error reading ATOM record for ZINC00002585 in ./xyz.mol2. WARNING read_mol2: Error reading ATOM record for ZINC00002588 in ./xyz.mol2. WARNING read_mol2: Error reading ATOM record for ZINC00002819 in ./xyz.mol2. WARNING read_mol2: Improper BOND origin/target for ZINC00003421 in ./xyz.mol2. and so on... ------------------------------------------------------------------------------------------ In this post, I will describe some highly odd results pertaining to one particular molecule that has been giving me the above error message. For one of the compounds in my mini-library, ZINC00014272, I received the above error message, and started further investigating why this particular molecule was not working. This molecule apparently has three separate .mol2 files. (By the way, what dictates whether a given molecule might have multiple .mol2, SDF, SMILES (etc.) file formats?? Various protonation states? Different conformers? Or simply, different programs that generate various .mol2 outputs? Why would ZINC00014272 contain three sub-entries?) Using these three different .mol2 files, I noticed that in my mini-library docking output (using DOCK 4.0.1), only the 2nd of the three molecules provided docking output (i.e. molecules #1 and #3 provided the above error message). I was curious as to why only #2 worked while #1 and #3 failed, so I started docking each of them individually and afterwards, in various combinations. I received highly odd results. The following represents the results that I got. Maybe one of you can make some sense of it: 1. Prior 3000 member library docking - #2 docked followed by an error message (presumably from molecule #3) 2. Docked only #1 - Docking failed and program crashed (mutilple computer address symbols showed up in the DOCK results. If you want further clarification as to this 'crashed output', I can show it to you in a subsequent post.) 3. Docked only #2 - Docking failed and program crashed. (I found this to be surprising since in my larger library, #2 was the only one that docked normally.) 4. Docked only #3 - Docking failed and program crashed. 5. Docked #1 followed by #2 - #2 docked fine, although #1 had no error message whatsoever. There were no error messages at all in the output. 6. Docked #1 followed by #3 - Docking failed and program crashed 7. Docked #2 followed by #3 - Docking failed and program crashed (Again, I found this quite surprising.) One error message was found in output. (My guess is that this is from #3) 8. Docked #2 followed by #1 - Docking failed and program crashed 9. Docked #1 followed by #2 followed by #3 - Exact same results as seen when docking the 3000-membered library. Only #2 docked properly, while #3 (presumably) gave the error message. 10. ZINC00012908 followed by #1 followed by #2 followed by #3 followed by ZINC00015788 - Same results as seen in scenario 9 (and scenario 1). However surprisingly, the two flanking molecules ZINC00012908 and ZINC00015788 had no noticeable output whatsoever, and was clearly not docked at all. It was as if these two molecules did not exist in the input .mol2 file at all. So these are my results, and I find myself incredibly confused as to why only #2 worked, why it had to work only following #1, and why the additional (flanking) compounds were not even found within the DOCK output and were certainly not docked. Again, this analysis was all performed using DOCK 4.0.1 . Perhaps switching to a newer version of DOCK might help too. However, I have already analyzed much of the results (the molecules that DID dock properly), and would rather focus on what I have, rather than to install the newer DOCK version. I would again appreciate any comments, focusing on the DOCK 4 output, rather than simply shifting immediately to DOCK 5 and/or 6. If anyone can provide any insight as to these highly peculiar results, I would absolutely appreciate it. Thank you very much in advance. Sincerely, Mike Silberstein From baoilleach at gmail.com Thu Jul 12 08:22:17 2007 From: baoilleach at gmail.com (Noel O'Boyle) Date: Thu, 12 Jul 2007 16:22:17 +0100 Subject: [Zinc-fans] Possible duplicates in ZINC Message-ID: Dear Dr. Irwin, I've been testing out Open Babel on the data in the first slice of the drug-like molecules subset of ZINC. The results are briefly discussed at: http://baoilleach.blogspot.com/2007/07/pybel-just-how-unique-are-your.html and http://baoilleach.blogspot.com/2007/07/pybel-just-how-unique-are-your_12.html In short, there appear to be a couple of cases of multiple duplicates. If you're interested in resolving this, I can send you off-list the ZINC IDs. I can also carry out this procedure for other datasets. Regards, Noel O'Boyle From jji at cgl.ucsf.edu Fri Jul 13 06:03:39 2007 From: jji at cgl.ucsf.edu (John J. Irwin) Date: Fri, 13 Jul 2007 06:03:39 -0700 Subject: [Zinc-fans] Possible duplicates in ZINC In-Reply-To: References: Message-ID: <4697782B.7020407@cgl.ucsf.edu> Hi Noel Thanks for your interest in ZINC, and your offer to help finding duplicates. We are well aware of this problem, and it is our aim to put it right. Please do send me your list (off the list). Thanks! John Noel O'Boyle wrote: > Dear Dr. Irwin, > > I've been testing out Open Babel on the data in the first slice of the > drug-like molecules subset of ZINC. The results are briefly discussed > at: > > http://baoilleach.blogspot.com/2007/07/pybel-just-how-unique-are-your.html > and > http://baoilleach.blogspot.com/2007/07/pybel-just-how-unique-are-your_12.html > > In short, there appear to be a couple of cases of multiple duplicates. > If you're interested in resolving this, I can send you off-list the > ZINC IDs. I can also carry out this procedure for other datasets. > > Regards, > Noel O'Boyle > _______________________________________________ > Zinc-fans mailing list > Zinc-fans at docking.org > http://blur.compbio.ucsf.edu/mailman/listinfo/zinc-fans > From jji at cgl.ucsf.edu Fri Jul 20 16:37:15 2007 From: jji at cgl.ucsf.edu (John J. Irwin) Date: Fri, 20 Jul 2007 16:37:15 -0700 Subject: [Zinc-fans] [Dock-fans] Error messages when docking specific molecules within ZINC-derived library In-Reply-To: References: Message-ID: <46A1472B.8040605@cgl.ucsf.edu> Hi Mike If you are using DOCK 4, are you adding the "substructure" record to the end of each mol2 entry as required? Two methods are referenced on the ZINC home page: http://blaster.docking.org/zinc/fix_substructure.py http://blaster.docking.org/zinc/zinc_convert.csh.txt If you are doing this already, please let me know and we will go on to the next step. Good luck! John Silberstein, Michael wrote: > Hi, > > I am a novice at docking larger libraries, and so, the following inquiry represents some of my current difficulties in docking (using DOCK 4.0.1) a ZINC-database derived mini-library. > > I have attempted to dock a library of ~3000 compounds to various zinc-metalloproteases. Even though 3000 separate molecules were included (in one large .mol2 file), only ~ 600 of them were able to provide docking results. The remaining 2400 compounds gave the following error: > > WARNING read_mol2: Error reading ATOM record for ZINC00001648 in ./xyz.mol2. > WARNING read_mol2: Error reading ATOM record for ZINC00001825 in ./xyz.mol2. > WARNING read_mol2: Improper BOND origin/target for ZINC00001932 in ./xyz.mol2. > WARNING read_mol2: Error reading ATOM record for ZINC00002585 in ./xyz.mol2. > WARNING read_mol2: Error reading ATOM record for ZINC00002588 in ./xyz.mol2. > WARNING read_mol2: Error reading ATOM record for ZINC00002819 in ./xyz.mol2. > WARNING read_mol2: Improper BOND origin/target for ZINC00003421 in ./xyz.mol2. > > and so on... > > Can anyone explain to me what might be wrong with the format of these individual .mol2 files such that either the ATOMs or BONDs cannot be read-in properly in order to have these molecules docked?? > > Since this analysis has been already performed using DOCK 4.0, it would be really good if I would not have to potentially repeat this using a newer version of DOCK. So it would be preferable if any suggestions/comments be regarding (specifically) DOCK 4.0 and why the program is having trouble reading in such a large percentage of ZINC database-derived .mol2 files. Any suggestion would be very helpful at this point. Thanks in advance. > > > Sincerely, > Mike Silberstein > > > _______________________________________________ > Dock-fans mailing list > Dock-fans at docking.org > http://blur.compbio.ucsf.edu/mailman/listinfo/dock-fans > From jji at cgl.ucsf.edu Fri Jul 20 17:20:29 2007 From: jji at cgl.ucsf.edu (John J. Irwin) Date: Fri, 20 Jul 2007 17:20:29 -0700 Subject: [Zinc-fans] help In-Reply-To: References: Message-ID: <46A1514D.8080802@cgl.ucsf.edu> Hi Filippo Thanks for your email. Filippo Marchioni wrote: > Dear ZINC users, > I am new on this mailing list and I hope my question will be > appropriate. > > I notice that in compounds like ZINC01607240 > (3-[4-[(4-amino-1,2-dimethyl-6-quinolyl)amino]-1,6-dimethyl-pyrimidin-2-yl]-1-(4-methoxyphenyl)-guanidine) > > the pyrimidin and the quinolin group are positively charged but the > charge assigned in the mol2 file for these two nitrogen still negative. > Am I completely missing the point or there is a problem? > There may well be a problem with this molecule. However, the one you describe is not it, I would say. The "charges" on the pyridine and the quinoline are formally +1, but the partial atomic charge as calculated at the semi-empirical level by AMSOL is delta negative. This is not inconsistent, and should not be surprising. For example, many atoms will have significant partial atomic charges (both + and -) and yet be formally uncharged in a lewis structure. Good luck! John > Thanks for your help > > best > Filippo > > _______________________________________________ > Zinc-fans mailing list > Zinc-fans at docking.org > http://blur.compbio.ucsf.edu/mailman/listinfo/zinc-fans >