http://wiki.docking.org/api.php?action=feedcontributions&user=JohnIrwin&feedformat=atomDISI - User contributions [en]2024-03-19T12:28:10ZUser contributionsMediaWiki 1.39.1http://wiki.docking.org/index.php?title=Talk:Old_Main&diff=5208Talk:Old Main2012-10-12T00:13:53Z<p>JohnIrwin: Created page with "We don't mind you using the talk pages, but if you notice a real problem, consider contacting Therese Demers or John Irwin to discuss."</p>
<hr />
<div>We don't mind you using the talk pages, but if you notice a real problem, consider contacting Therese Demers or John Irwin to discuss.</div>JohnIrwinhttp://wiki.docking.org/index.php?title=User:JohnIrwin&diff=5206User:JohnIrwin2012-10-12T00:06:15Z<p>JohnIrwin: Created page with "John Irwin"</p>
<hr />
<div>John Irwin</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:Errata&diff=4788ZINC:Errata2007-12-19T21:50:20Z<p>JohnIrwin: </p>
<hr />
<div>Here are errata as reported for ZINC:<br />
<br />
<br />
* for SIGMA propiophenone [http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/P51605 P51605] ZINC has 1671385 entry, and the ring in it does not show as aromatic.<br />
** FIXED on 12/18/07<br />
<br />
* many molecules reported with ZINC01278699. Sorry about this case. It will be removed in the next version.<br />
<br />
* the following pairs are not identical, but actually different protonation states of hydroxamic acids (looks like PipelinePilot has a problem interpreting the mol2 files, I rechecked everything with the sdf files): ZINC03817650, ZINC04628541; ZINC01548784, ZINC03820719 <br />
<br />
* I downloaded the databases Asinex and Sigma-aldrich from the version 7 <br />
of ZINC in both the formats SMILES and MOL2. For both the databases I <br />
found a difference in the molecules present in the archives, that means <br />
some molecules present in the multi-mol2 file and not in the SMILES and <br />
vice versa. Is it possible or I did some errors in the comparison?<br />
<br />
No, you are quite correct. I just did:<br />
> zmore sial_p0.smi.gz | awk '{print $2}' | sort -u > smiles_codes <br />
> zcat sial_p0.?.mol2.gz | grep ZINC | sort -u > mol2_p0_codes<br />
> wc -l smiles_codes mol2_p0_codes<br />
114763 smiles_codes<br />
112069 mol2_p0_codes<br />
> diff smiles_codes mol2_p0_codes |wc -l<br />
4265<br />
<br />
I agree that there are a little over 2,500 differences in the mol2 and SMILES of Sigma Aldrich in ZINC version 7, a little over 2% of the library.<br />
<br />
<br />
<br />
* There appears to be an issue with isomerism in the ZINC database, which affects DUD. An example is compounds 3165371 and 4460991. These are E/Z isomers around a double bond. If you ask for the SMILES strings, these match the 2D depictions you see on the search results page (not suprising, really, as I imagine that the 2D depictions are generated directly from the SMILES). However, if you ask for these compounds as SDF files, you get the correct isomer of 4460991, but you get two structures for 3165371, both of which are wrong compared to the SMILES (one is identical to 4460991, and the other has the exocyclic double bond flipped).<br />
<br />
Both of these compounds are in the DUD data set. However, since the SDF data available for 3165371 are incorrect, the DUD data set has ended up with duplicate structures.<br />
<br />
We believe there are several cases of this in DUD (and ZINC). E/Z isomerism has been a sore point for us ever since we got started. We are aware of this problem, and aim to fix as many of these problems as possible in the next release. I think the SDF should be taken as authoritative over the SMILES, if they disagree. However, we have not yet been able to make a complete study of this.<br />
<br />
<br />
[[Category:Errata]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC8:Release_notes&diff=4767ZINC8:Release notes2007-12-19T18:08:28Z<p>JohnIrwin: </p>
<hr />
<div>Release notes for ZINC version 8, released in January 2008.<br />
{{TOCright}}<br />
= Features = <br />
== New vendors ==<br />
* Adesis<br />
* Asymchem<br />
* Biosynth<br />
* CiVentiChem<br />
* SynQuest<br />
* Zannan<br />
(there are at least 6 more John)<br />
<br />
== New database sources ==<br />
* MLSMR<br />
* NCI plated 2007<br />
<br />
== New compounds ==<br />
* Over 10 M compounds total<br />
* 7M purchasable with zero rule of 5 violations<br />
* 1.1M purchasable with zero "rule of 3.5" violations aka "lead-like"<br />
* 63K purchasable with zero "rule of 2.5" violations aka "frag-like"<br />
<br />
== New look and feel ==<br />
* css pull down menus for easier navigation<br />
* <br />
<br />
== New features ==<br />
* all new upload feature<br />
* XML RPC support for uploads<br />
* new often-requested subsets<br />
* <br />
<br />
= Fixes =<br />
<br />
== Broken molecules ==<br />
* one<br />
<br />
== Duplicates ==<br />
* one<br />
<br />
== Subsetting ==<br />
* one<br />
<br />
== Uploading ==<br />
* one<br />
<br />
== Discontinued vendors ==<br />
* Chemstar<br />
<br />
<br />
[[Category:Release notes]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC8:Release_notes&diff=4766ZINC8:Release notes2007-12-19T18:07:52Z<p>JohnIrwin: </p>
<hr />
<div>Release notes for ZINC version 8, released in January 2008.<br />
<br />
= Features = <br />
== New vendors ==<br />
* Adesis<br />
* Asymchem<br />
* Biosynth<br />
* CiVentiChem<br />
* SynQuest<br />
* Zannan<br />
(there are at least 6 more John)<br />
<br />
== New database sources ==<br />
* MLSMR<br />
* NCI plated 2007<br />
<br />
== New compounds ==<br />
* Over 10 M compounds total<br />
* 7M purchasable with zero rule of 5 violations<br />
* 1.1M purchasable with zero "rule of 3.5" violations aka "lead-like"<br />
* 63K purchasable with zero "rule of 2.5" violations aka "frag-like"<br />
<br />
== New look and feel ==<br />
* css pull down menus for easier navigation<br />
* <br />
<br />
== New features ==<br />
* all new upload feature<br />
* XML RPC support for uploads<br />
* new often-requested subsets<br />
* <br />
<br />
= Fixes =<br />
<br />
== Broken molecules ==<br />
* one<br />
<br />
== Duplicates ==<br />
* one<br />
<br />
== Subsetting ==<br />
* one<br />
<br />
== Uploading ==<br />
* one<br />
<br />
== Discontinued vendors ==<br />
* Chemstar<br />
<br />
<br />
[[Category:Release notes]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=How_to_cite&diff=3193How to cite2007-12-13T23:38:13Z<p>JohnIrwin: </p>
<hr />
<div>HOW TO CITE<br />
<br />
= ZINC = <br />
Irwin and Shoichet, J. Chem. Inf. Model. 2005;45(1):177-82<br />
<br />
= DUD = <br />
Huang, Shoichet and Irwin, J. Med. Chem., 2006, 49(23), 6789-6801.<br />
<br />
= DOCK Blaster = <br />
Huang, Shoichet and Irwin, J. Med. Chem., 2006, 49(23), 6789-6801 (for now). Will be published in 2008.<br />
<br />
= DOCK 6 = <br />
Moustakas DT, Lang PT, Pegg S, Pettersen E, Kuntz ID, Brooijmans N, Rizzo RC. J Comput Aided Mol Des. 2006 Oct-Nov;20(10-11):601-19<br />
<br />
= DOCK 3.5.54 = <br />
Lorber DM, Shoichet BK. Hierarchical docking of databases of multiple ligand conformations. Curr Top Med Chem 5 (8), 739-49 (2005).<br />
<br />
Lorber DM, Shoichet BK. Flexible ligand docking using conformational ensembles. Protein Science 7, 938-950 (1998).<br />
<br />
Wei BQ, Baase WA, Weaver LH, Matthews BW, Shoichet BK. A model binding site for testing scoring functions in molecular docking. J Mol Biol 322, 339-55 (2002).<br />
<br />
Meng EC, Shoichet BK, Kuntz ID. Automated docking with grid-based energy evaluation. Journal of Computational Chemistry 13, 505-524 (1992). <br />
<br />
<br />
= SEA = <br />
Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotech 25 (2), 197-206 (2007).<br />
<br />
= HEI = <br />
Hermann JC, Ghanem E, Li Y, Raushel FM, Irwin JJ and Shoichet BK, Predicting substrates by docking high-energy intermediates to enzyme substuctures. J Am Chem Soc. 128, 15882-91 (2006).<br />
<br />
<br />
[[Category:Publications]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_5&diff=644DOCK 52007-12-13T17:27:14Z<p>JohnIrwin: </p>
<hr />
<div>DOCK 5 is superseded by [[DOCK 6]].</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ODOSOS&diff=3823ODOSOS2007-12-11T05:20:23Z<p>JohnIrwin: </p>
<hr />
<div>ODOSOS is the acronym for [[open data]], [[open source]], [[open standards]]. Don't you hate these sorts of acronyms?<br />
<br />
The products of docking.org are open in the limited "free as in beer" sense. That is, ZINC and DUD may be downloaded freely. DOCK Blaster may be used without charge. This wiki may be freely edited (after registration). <br />
<br />
<br />
[[Category:Acronyms]]<br />
[[Category:Jargon]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=SEA&diff=4289SEA2007-12-11T05:11:43Z<p>JohnIrwin: </p>
<hr />
<div>SEA, the similarity ensemble approach. <br />
[http://sea.docking.org sea.docking.org]<br />
<br />
<br />
<br />
[[Category:SEA]]<br />
[[Category:Scaffold hopping]]<br />
[[Category:Off target effects]]<br />
[[Category:Pharmacology]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1139DUD:Errata2007-12-07T01:47:02Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
All errors reported at cataloged here. Feel free to add your own. We aim to fix all of these problems in the next release. Thank you to helpful investigators who wrote us email advising us of these problems. We have kept you anonymous. You are welcome to add your name here if you like.<br />
<br />
= General = <br />
<br />
* In the DUD paper, J Med Chem 2006, Huang, Shoichet, Irwin, jm0608356. The PDB id of ADA in table1 is wrong. It should be "1ndw", not "1stw". Our final version submitted was correct, but we failed to catch this in the galleys. <br />
<br />
* Q: Why is the ratio of decoys to annotated ligands described as 36 to 1 in the paper, yet there are on average only 33 to 1 in DUD? This is due to overlap, as the same decoy could be used for multiple targets, particularly in the kinase class where there was so much overlap.<br />
<br />
* Two DUD decoy compounds (ZINC154632 for RXR decoys and ZINC608655 for ER decoys) were structurally identical/similar to the crystal ligands of RXR and ER, individually. This problem was caused by failing to include the crystallographic ligands in our annotated ligands set, and will be fixed in the next version of DUD. Thanks to Paul Hawkins of OpenEye for bringing this to our attention.<br />
<br />
* Also: PDB code for COX-1 structure in given as 1P4G but should be 1Q4G. We regret this error, and thank alert reader Paul Hawkins of OpenEye for this information Also, Hao Li of UCSF Pharm Chem points out that the PDB id of ADA in the paper is wrong. It should be 1ndw. <br />
<br />
= Factor Xa =<br />
* These each have amidine groups that have been over-protonated so that<br />
the amidine is no longer a planar Nsp2-Csp2-Nsp2 structure: ZINC03831927, 04629420, 04633281<br />
<br />
* This ligand has a piperazine group that is doubly protonated. In vivo<br />
either single protonation or (possibly) no protonation at all would be<br />
the norm. I don't believe the alternative structures are in the active set: ZINC03815578<br />
<br />
* These structures all have suspicious protonated dihydropyridine<br />
structures. Such an unstable substructure is most unlikely to be present<br />
in a stable Factor Xa ligand as it would very rapidly oxidatively<br />
aromatise to the protonated pyridine. Therefore I suspect that these<br />
substructures are all incorrect: ZINC03815848, 3814850, 4631018, 4631023, 4631034<br />
<br />
= thrombin = <br />
<br />
* For thrombin_decoys.mol2 and thrombin_ligands.mol2, there seems to be something wrong with the protonation of certain amidines: the groups are doubly protonated and hydrogenated as well, resulting in C([NH3+])[NH3+], with a now tetraedric C atom. Found in the ligands set for ZINC03834109, ZINC03834111, ZINC03834112, ZINC03834113, ZINC03834114, ZINC03834115, ZINC04617937, ZINC04617938, ZINC04617939, ZINC04617940.<br />
<br />
I've found some names (124) multiple times. Most of them describe different tautomeric and protonation states (I'm still undecided if I would prefer those to have different names...). However, for 18 such pairs I also found identical canonical smiles, so I would count them as duplicates. Ligands: ZINC03815818, ZINC04617938, ZINC04617939, ZINC04617940. Decoys: ZINC03935806, ZINC03931773, ZINC03820759, ZINC03818898, ZINC03818733, ZINC03045673, ZINC02877078, ZINC02877076, ZINC02877075, ZINC02717771, ZINC01066121, ZINC00781033, ZINC00588653, ZINC00579389.<br />
<br />
* Furthermore, I found 20 pairs of compounds in the decoy set, that have different names but identical canonical smiles:<br />
ZINC03998885, ZINC04467871<br />
ZINC03974519, ZINC04469531<br />
ZINC03890055, ZINC04464875<br />
ZINC03889994, ZINC04464852<br />
ZINC03889707, ZINC04464762<br />
ZINC03867866, ZINC04465782<br />
ZINC03867594, ZINC04465649<br />
ZINC03867505, ZINC04465603<br />
ZINC03859006, ZINC04468426<br />
ZINC03857957, ZINC04469620<br />
ZINC03857648, ZINC04464507<br />
ZINC03857636, ZINC04464501<br />
ZINC03857579, ZINC04464474<br />
ZINC03857293, ZINC04464286<br />
ZINC03857182, ZINC04464189<br />
ZINC03857181, ZINC04464188<br />
ZINC03817650, ZINC04628541<br />
ZINC02686537, ZINC03892786<br />
ZINC01548784, ZINC03820719<br />
ZINC01040460, ZINC01040461<br />
<br />
I checked a few of these duplicates manually and found identical 3D structures, though sometimes different atom numbering - compare for example ZINC01040460 and ZINC01040461.<br />
<br />
* Doubtful compounds where the amidino group is not planar, ZINC names of thrombin dud_ligands2006: 03834109, 03834111, 03834112, 03834113, 03834114, 03834115, 04617937, 04617938, 04617939<br />
<br />
= trypsin =<br />
* In structures ZINC03815826, ZINC03834185, and ZINC04617941(for example), there are C(-[N+])-[N+] substructures. My medicinal chemistry colleagues assure me that (a) these are not stable, and (b) if they were stable they wouldn't be double-protonated. Is it possible that these should actually be amidines and have been drawn incorrectly? The supplier for these is listed as 'DUD', so there's no definitive chemical supplier to check with. There are a number of these in the dataset, so would significantly affect the results...<br />
<br />
<br />
<br />
See also: [[ZINC:Errata]]<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:Errata&diff=4787ZINC:Errata2007-12-07T00:53:22Z<p>JohnIrwin: </p>
<hr />
<div>Here are errata as reported for ZINC:<br />
<br />
<br />
* for SIGMA propiophenone [http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/P51605 P51605] ZINC has 1671385 entry, and the ring in it does not show as aromatic.<br />
<br />
* many molecules reported with ZINC01278699. Sorry about this case. It will be removed in the next version.<br />
<br />
* the following pairs are not identical, but actually different protonation states of hydroxamic acids (looks like PipelinePilot has a problem interpreting the mol2 files, I rechecked everything with the sdf files): ZINC03817650, ZINC04628541; ZINC01548784, ZINC03820719 <br />
<br />
* I downloaded the databases Asinex and Sigma-aldrich from the version 7 <br />
of ZINC in both the formats SMILES and MOL2. For both the databases I <br />
found a difference in the molecules present in the archives, that means <br />
some molecules present in the multi-mol2 file and not in the SMILES and <br />
vice versa. Is it possible or I did some errors in the comparison?<br />
<br />
No, you are quite correct. I just did:<br />
> zmore sial_p0.smi.gz | awk '{print $2}' | sort -u > smiles_codes <br />
> zcat sial_p0.?.mol2.gz | grep ZINC | sort -u > mol2_p0_codes<br />
> wc -l smiles_codes mol2_p0_codes<br />
114763 smiles_codes<br />
112069 mol2_p0_codes<br />
> diff smiles_codes mol2_p0_codes |wc -l<br />
4265<br />
<br />
I agree that there are a little over 2,500 differences in the mol2 and SMILES of Sigma Aldrich in ZINC version 7, a little over 2% of the library.<br />
<br />
<br />
<br />
* There appears to be an issue with isomerism in the ZINC database, which affects DUD. An example is compounds 3165371 and 4460991. These are E/Z isomers around a double bond. If you ask for the SMILES strings, these match the 2D depictions you see on the search results page (not suprising, really, as I imagine that the 2D depictions are generated directly from the SMILES). However, if you ask for these compounds as SDF files, you get the correct isomer of 4460991, but you get two structures for 3165371, both of which are wrong compared to the SMILES (one is identical to 4460991, and the other has the exocyclic double bond flipped).<br />
<br />
Both of these compounds are in the DUD data set. However, since the SDF data available for 3165371 are incorrect, the DUD data set has ended up with duplicate structures.<br />
<br />
We believe there are several cases of this in DUD (and ZINC). E/Z isomerism has been a sore point for us ever since we got started. We are aware of this problem, and aim to fix as many of these problems as possible in the next release. I think the SDF should be taken as authoritative over the SMILES, if they disagree. However, we have not yet been able to make a complete study of this.<br />
<br />
<br />
[[Category:Errata]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1138DUD:Errata2007-12-07T00:48:46Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
All errors reported at cataloged here. Feel free to add your own. We aim to fix all of these problems in the next release. Thank you to helpful investigators who wrote us email advising us of these problems. We have kept you anonymous. You are welcome to add your name here if you like.<br />
<br />
= General = <br />
<br />
* In the DUD paper, J Med Chem 2006, Huang, Shoichet, Irwin, jm0608356. The PDB id of ADA in table1 is wrong. It should be "1ndw", not "1stw". Our final version submitted was correct, but we failed to catch this in the galleys. <br />
<br />
* Q: Why is the ratio of decoys to annotated ligands described as 36 to 1 in the paper, yet there are on average only 33 to 1 in DUD? This is due to overlap, as the same decoy could be used for multiple targets, particularly in the kinase class where there was so much overlap.<br />
<br />
* Two DUD decoy compounds (ZINC154632 for RXR decoys and ZINC608655 for ER decoys) were structurally identical/similar to the crystal ligands of RXR and ER, individually. This problem was caused by failing to include the crystallographic ligands in our annotated ligands set, and will be fixed in the next version of DUD. Thanks to Paul Hawkins of OpenEye for bringing this to our attention.<br />
<br />
* Also: PDB code for COX-1 structure in given as 1P4G but should be 1Q4G. We regret this error, and thank alert reader Paul Hawkins of OpenEye for this information Also, Hao Li of UCSF Pharm Chem points out that the PDB id of ADA in the paper is wrong. It should be 1ndw. <br />
<br />
= Factor Xa =<br />
* These each have amidine groups that have been over-protonated so that<br />
the amidine is no longer a planar Nsp2-Csp2-Nsp2 structure: ZINC03831927, 04629420, 04633281<br />
<br />
* This ligand has a piperazine group that is doubly protonated. In vivo<br />
either single protonation or (possibly) no protonation at all would be<br />
the norm. I don't believe the alternative structures are in the active set: ZINC03815578<br />
<br />
* These structures all have suspicious protonated dihydropyridine<br />
structures. Such an unstable substructure is most unlikely to be present<br />
in a stable Factor Xa ligand as it would very rapidly oxidatively<br />
aromatise to the protonated pyridine. Therefore I suspect that these<br />
substructures are all incorrect: ZINC03815848, 3814850, 4631018, 4631023, 4631034<br />
<br />
= thrombin = <br />
<br />
* For thrombin_decoys.mol2 and thrombin_ligands.mol2, there seems to be something wrong with the protonation of certain amidines: the groups are doubly protonated and hydrogenated as well, resulting in C([NH3+])[NH3+], with a now tetraedric C atom. Found in the ligands set for ZINC03834109, ZINC03834111, ZINC03834112, ZINC03834113, ZINC03834114, ZINC03834115, ZINC04617937, ZINC04617938, ZINC04617939, ZINC04617940.<br />
<br />
I've found some names (124) multiple times. Most of them describe different tautomeric and protonation states (I'm still undecided if I would prefer those to have different names...). However, for 18 such pairs I also found identical canonical smiles, so I would count them as duplicates. Ligands: ZINC03815818, ZINC04617938, ZINC04617939, ZINC04617940. Decoys: ZINC03935806, ZINC03931773, ZINC03820759, ZINC03818898, ZINC03818733, ZINC03045673, ZINC02877078, ZINC02877076, ZINC02877075, ZINC02717771, ZINC01066121, ZINC00781033, ZINC00588653, ZINC00579389.<br />
<br />
* Furthermore, I found 20 pairs of compounds in the decoy set, that have different names but identical canonical smiles:<br />
ZINC03998885, ZINC04467871<br />
ZINC03974519, ZINC04469531<br />
ZINC03890055, ZINC04464875<br />
ZINC03889994, ZINC04464852<br />
ZINC03889707, ZINC04464762<br />
ZINC03867866, ZINC04465782<br />
ZINC03867594, ZINC04465649<br />
ZINC03867505, ZINC04465603<br />
ZINC03859006, ZINC04468426<br />
ZINC03857957, ZINC04469620<br />
ZINC03857648, ZINC04464507<br />
ZINC03857636, ZINC04464501<br />
ZINC03857579, ZINC04464474<br />
ZINC03857293, ZINC04464286<br />
ZINC03857182, ZINC04464189<br />
ZINC03857181, ZINC04464188<br />
ZINC03817650, ZINC04628541<br />
ZINC02686537, ZINC03892786<br />
ZINC01548784, ZINC03820719<br />
ZINC01040460, ZINC01040461<br />
<br />
I checked a few of these duplicates manually and found identical 3D structures, though sometimes different atom numbering - compare for example ZINC01040460 and ZINC01040461.<br />
<br />
<br />
= trypsin =<br />
* In structures ZINC03815826, ZINC03834185, and ZINC04617941(for example), there are C(-[N+])-[N+] substructures. My medicinal chemistry colleagues assure me that (a) these are not stable, and (b) if they were stable they wouldn't be double-protonated. Is it possible that these should actually be amidines and have been drawn incorrectly? The supplier for these is listed as 'DUD', so there's no definitive chemical supplier to check with. There are a number of these in the dataset, so would significantly affect the results...<br />
<br />
<br />
See also: [[ZINC:Errata]]<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1137DUD:Errata2007-12-07T00:44:59Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
* In the DUD paper, J Med Chem 2006, Huang, Shoichet, Irwin, jm0608356. The PDB id of ADA in table1 is wrong. It should be "1ndw", not "1stw". Our final version submitted was correct, but we failed to catch this in the galleys. <br />
<br />
* Q: Why is the ratio of decoys to annotated ligands described as 36 to 1 in the paper, yet there are on average only 33 to 1 in DUD? This is due to overlap, as the same decoy could be used for multiple targets, particularly in the kinase class where there was so much overlap.<br />
<br />
* Two DUD decoy compounds (ZINC154632 for RXR decoys and ZINC608655 for ER decoys) were structurally identical/similar to the crystal ligands of RXR and ER, individually. This problem was caused by failing to include the crystallographic ligands in our annotated ligands set, and will be fixed in the next version of DUD. Thanks to Paul Hawkins of OpenEye for bringing this to our attention.<br />
<br />
* Also: PDB code for COX-1 structure in given as 1P4G but should be 1Q4G. We regret this error, and thank alert reader Paul Hawkins of OpenEye for this information Also, Hao Li of UCSF Pharm Chem points out that the PDB id of ADA in the paper is wrong. It should be 1ndw. <br />
<br />
= Factor Xa =<br />
* These each have amidine groups that have been over-protonated so that<br />
the amidine is no longer a planar Nsp2-Csp2-Nsp2 structure: ZINC03831927, 04629420, 04633281<br />
<br />
* This ligand has a piperazine group that is doubly protonated. In vivo<br />
either single protonation or (possibly) no protonation at all would be<br />
the norm. I don't believe the alternative structures are in the active set: ZINC03815578<br />
<br />
* These structures all have suspicious protonated dihydropyridine<br />
structures. Such an unstable substructure is most unlikely to be present<br />
in a stable Factor Xa ligand as it would very rapidly oxidatively<br />
aromatise to the protonated pyridine. Therefore I suspect that these<br />
substructures are all incorrect: ZINC03815848, 3814850, 4631018, 4631023, 4631034<br />
<br />
= thrombin = <br />
<br />
* For thrombin_decoys.mol2 and thrombin_ligands.mol2, there seems to be something wrong with the protonation of certain amidines: the groups are doubly protonated and hydrogenated as well, resulting in C([NH3+])[NH3+], with a now tetraedric C atom. Found in the ligands set for ZINC03834109, ZINC03834111, ZINC03834112, ZINC03834113, ZINC03834114, ZINC03834115, ZINC04617937, ZINC04617938, ZINC04617939, ZINC04617940.<br />
<br />
I've found some names (124) multiple times. Most of them describe different tautomeric and protonation states (I'm still undecided if I would prefer those to have different names...). However, for 18 such pairs I also found identical canonical smiles, so I would count them as duplicates. Ligands: ZINC03815818, ZINC04617938, ZINC04617939, ZINC04617940. Decoys: ZINC03935806, ZINC03931773, ZINC03820759, ZINC03818898, ZINC03818733, ZINC03045673, ZINC02877078, ZINC02877076, ZINC02877075, ZINC02717771, ZINC01066121, ZINC00781033, ZINC00588653, ZINC00579389.<br />
<br />
* Furthermore, I found 20 pairs of compounds in the decoy set, that have different names but identical canonical smiles:<br />
ZINC03998885, ZINC04467871<br />
ZINC03974519, ZINC04469531<br />
ZINC03890055, ZINC04464875<br />
ZINC03889994, ZINC04464852<br />
ZINC03889707, ZINC04464762<br />
ZINC03867866, ZINC04465782<br />
ZINC03867594, ZINC04465649<br />
ZINC03867505, ZINC04465603<br />
ZINC03859006, ZINC04468426<br />
ZINC03857957, ZINC04469620<br />
ZINC03857648, ZINC04464507<br />
ZINC03857636, ZINC04464501<br />
ZINC03857579, ZINC04464474<br />
ZINC03857293, ZINC04464286<br />
ZINC03857182, ZINC04464189<br />
ZINC03857181, ZINC04464188<br />
ZINC03817650, ZINC04628541<br />
ZINC02686537, ZINC03892786<br />
ZINC01548784, ZINC03820719<br />
ZINC01040460, ZINC01040461<br />
<br />
I checked a few of these duplicates manually and found identical 3D structures, though sometimes different atom numbering - compare for example ZINC01040460 and ZINC01040461.<br />
<br />
See also: [[ZINC:Errata]]<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1136DUD:Errata2007-12-07T00:44:08Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
* In the DUD paper, J Med Chem 2006, Huang, Shoichet, Irwin, jm0608356. The PDB id of ADA in table1 is wrong. It should be "1ndw", not "1stw". Our final version submitted was correct, but we failed to catch this in the galleys. <br />
<br />
* Q: Why is the ratio of decoys to annotated ligands described as 36 to 1 in the paper, yet there are on average only 33 to 1 in DUD? This is due to overlap, as the same decoy could be used for multiple targets, particularly in the kinase class where there was so much overlap.<br />
<br />
* Two DUD decoy compounds (ZINC154632 for RXR decoys and ZINC608655 for ER decoys) were structurally identical/similar to the crystal ligands of RXR and ER, individually. This problem was caused by failing to include the crystallographic ligands in our annotated ligands set, and will be fixed in the next version of DUD. Thanks to Paul Hawkins of OpenEye for bringing this to our attention.<br />
<br />
* Also: PDB code for COX-1 structure in given as 1P4G but should be 1Q4G. We regret this error, and thank alert reader Paul Hawkins of OpenEye for this information Also, Hao Li of UCSF Pharm Chem points out that the PDB id of ADA in the paper is wrong. It should be 1ndw. <br />
<br />
= Factor Xa =<br />
* These each have amidine groups that have been over-protonated so that<br />
the amidine is no longer a planar Nsp2-Csp2-Nsp2 structure: ZINC03831927, 04629420, 04633281<br />
<br />
* This ligand has a piperazine group that is doubly protonated. In vivo<br />
either single protonation or (possibly) no protonation at all would be<br />
the norm. I don't believe the alternative structures are in the active set: ZINC03815578<br />
<br />
* These structures all have suspicious protonated dihydropyridine<br />
structures. Such an unstable substructure is most unlikely to be present<br />
in a stable Factor Xa ligand as it would very rapidly oxidatively<br />
aromatise to the protonated pyridine. Therefore I suspect that these<br />
substructures are all incorrect: ZINC03815848, 3814850, 4631018, 4631023, 4631034<br />
<br />
* For thrombin_decoys.mol2 and thrombin_ligands.mol2, there seems to be something wrong with the protonation of certain amidines: the groups are doubly protonated and hydrogenated as well, resulting in C([NH3+])[NH3+], with a now tetraedric C atom. Found in the ligands set for ZINC03834109, ZINC03834111, ZINC03834112, ZINC03834113, ZINC03834114, ZINC03834115, ZINC04617937, ZINC04617938, ZINC04617939, ZINC04617940.<br />
<br />
I've found some names (124) multiple times. Most of them describe different tautomeric and protonation states (I'm still undecided if I would prefer those to have different names...). However, for 18 such pairs I also found identical canonical smiles, so I would count them as duplicates. Ligands: ZINC03815818, ZINC04617938, ZINC04617939, ZINC04617940. Decoys: ZINC03935806, ZINC03931773, ZINC03820759, ZINC03818898, ZINC03818733, ZINC03045673, ZINC02877078, ZINC02877076, ZINC02877075, ZINC02717771, ZINC01066121, ZINC00781033, ZINC00588653, ZINC00579389.<br />
<br />
* Furthermore, I found 20 pairs of compounds in the decoy set, that have different names but identical canonical smiles:<br />
ZINC03998885, ZINC04467871<br />
ZINC03974519, ZINC04469531<br />
ZINC03890055, ZINC04464875<br />
ZINC03889994, ZINC04464852<br />
ZINC03889707, ZINC04464762<br />
ZINC03867866, ZINC04465782<br />
ZINC03867594, ZINC04465649<br />
ZINC03867505, ZINC04465603<br />
ZINC03859006, ZINC04468426<br />
ZINC03857957, ZINC04469620<br />
ZINC03857648, ZINC04464507<br />
ZINC03857636, ZINC04464501<br />
ZINC03857579, ZINC04464474<br />
ZINC03857293, ZINC04464286<br />
ZINC03857182, ZINC04464189<br />
ZINC03857181, ZINC04464188<br />
ZINC03817650, ZINC04628541<br />
ZINC02686537, ZINC03892786<br />
ZINC01548784, ZINC03820719<br />
ZINC01040460, ZINC01040461<br />
<br />
I checked a few of these duplicates manually and found identical 3D structures, though sometimes different atom numbering - compare for example ZINC01040460 and ZINC01040461.<br />
<br />
See also: [[ZINC:Errata]]<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:Errata&diff=4786ZINC:Errata2007-12-07T00:41:01Z<p>JohnIrwin: </p>
<hr />
<div>Here are errata as reported for ZINC:<br />
<br />
<br />
* for SIGMA propiophenone [http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/P51605 P51605] ZINC has 1671385 entry, and the ring in it does not show as aromatic.<br />
<br />
* many molecules reported with ZINC01278699. Sorry about this case. It will be removed in the next version.<br />
<br />
* the following pairs are not identical, but actually different protonation states of hydroxamic acids (looks like PipelinePilot has a problem interpreting the mol2 files, I rechecked everything with the sdf files): ZINC03817650, ZINC04628541; ZINC01548784, ZINC03820719 <br />
<br />
* I downloaded the databases Asinex and Sigma-aldrich from the version 7 <br />
of ZINC in both the formats SMILES and MOL2. For both the databases I <br />
found a difference in the molecules present in the archives, that means <br />
some molecules present in the multi-mol2 file and not in the SMILES and <br />
vice versa. Is it possible or I did some errors in the comparison?<br />
<br />
No, you are quite correct. I just did:<br />
> zmore sial_p0.smi.gz | awk '{print $2}' | sort -u > smiles_codes <br />
> zcat sial_p0.?.mol2.gz | grep ZINC | sort -u > mol2_p0_codes<br />
> wc -l smiles_codes mol2_p0_codes<br />
114763 smiles_codes<br />
112069 mol2_p0_codes<br />
> diff smiles_codes mol2_p0_codes |wc -l<br />
4265<br />
<br />
I agree that there are a little over 2,500 differences in the mol2 and SMILES of Sigma Aldrich in ZINC version 7, a little over 2% of the library.<br />
<br />
[[Category:Errata]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:Errata&diff=4785ZINC:Errata2007-12-06T22:35:29Z<p>JohnIrwin: </p>
<hr />
<div>Here are errata as reported for ZINC:<br />
<br />
<br />
* for SIGMA propiophenone [http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/P51605 P51605] ZINC has 1671385 entry, and the ring in it does not show as aromatic.<br />
<br />
* many molecules reported with ZINC01278699. Sorry about this case. It will be removed in the next version.<br />
<br />
<br />
* I downloaded the databases Asinex and Sigma-aldrich from the version 7 <br />
of ZINC in both the formats SMILES and MOL2. For both the databases I <br />
found a difference in the molecules present in the archives, that means <br />
some molecules present in the multi-mol2 file and not in the SMILES and <br />
vice versa. Is it possible or I did some errors in the comparison?<br />
<br />
No, you are quite correct. I just did:<br />
> zmore sial_p0.smi.gz | awk '{print $2}' | sort -u > smiles_codes <br />
> zcat sial_p0.?.mol2.gz | grep ZINC | sort -u > mol2_p0_codes<br />
> wc -l smiles_codes mol2_p0_codes<br />
114763 smiles_codes<br />
112069 mol2_p0_codes<br />
> diff smiles_codes mol2_p0_codes |wc -l<br />
4265<br />
<br />
I agree that there are a little over 2,500 differences in the mol2 and SMILES of Sigma Aldrich in ZINC version 7, a little over 2% of the library.<br />
<br />
[[Category:Errata]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:FAQ&diff=4792ZINC:FAQ2007-12-06T22:27:33Z<p>JohnIrwin: </p>
<hr />
<div>Here are frequently asked questions about ZINC.<br />
<br />
<br />
Q1. I am trying to generate a subset of your "drug-like" molecule subset for<br />
virtual screening. I was thinking your 60% diversity group (about 12,000<br />
molecules) would be a place to start, and I downloaded the .smi file. I<br />
relatively new to chemoinformatics and I was wondering if there is an<br />
elegant way to separate the compounds listed in the .smi file from the<br />
larger library containing the mol2 files from the 2,000,000 "usual" set that<br />
I have downloaded from ZINC?<br />
<br />
A1.<br />
wget http://zinc8.docking.org/subset1/3/3_t60.smi<br />
awk '{print $2}' 3_t60.smi >! codes<br />
sed -e 's/^/fget2.pl?f=m\&l=0\&z=/' codes > codes2<br />
wget -O all.mol2 -a listing -B http://zinc8.docking.org/ -i codes2<br />
<br />
<br />
Note this currently only gets a single (pH 7) representation of each molecule.<br />
<br />
<br />
[[Category:FAQ]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:FAQ&diff=4791ZINC:FAQ2007-12-06T22:26:54Z<p>JohnIrwin: </p>
<hr />
<div>Here are frequently asked questions about ZINC.<br />
<br />
<br />
Q1. I am trying to generate a subset of your "drug-like" molecule subset for<br />
virtual screening. I was thinking your 60% diversity group (about 12,000<br />
molecules) would be a place to start, and I downloaded the .smi file. I<br />
relatively new to chemoinformatics and I was wondering if there is an<br />
elegant way to separate the compounds listed in the .smi file from the<br />
larger library containing the mol2 files from the 2,000,000 "usual" set that<br />
I have downloaded from ZINC?<br />
<br />
A1.<br />
wget http://zinc8.docking.org/subset1/3/3_t60.smi<br />
awk '{print $2}' 3_t60.smi >! codes<br />
sed -e 's/^/fget2.pl?f=m\&l=0\&z=/' codes > codes2<br />
wget -O all.mol2 -a listing -B http://zinc8.docking.org/ -i codes2<br />
<br />
<br />
[[Category:FAQ]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:Errata&diff=4784ZINC:Errata2007-12-06T20:25:15Z<p>JohnIrwin: </p>
<hr />
<div>Here are errata as reported for ZINC:<br />
<br />
<br />
* for SIGMA propiophenone [http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/P51605 P51605] ZINC has 1671385 entry, and the ring in it does not show as aromatic.<br />
<br />
* many molecules reported with ZINC01278699. Sorry about this case. It will be removed in the next version.<br />
<br />
[[Category:Errata]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:FAQ&diff=4790ZINC:FAQ2007-12-06T20:24:58Z<p>JohnIrwin: </p>
<hr />
<div>Here are frequently asked questions about ZINC.</div>JohnIrwinhttp://wiki.docking.org/index.php?title=ZINC:Errata&diff=4783ZINC:Errata2007-12-06T20:12:05Z<p>JohnIrwin: </p>
<hr />
<div>Here are errata as reported for ZINC:<br />
<br />
<br />
* for SIGMA propiophenone [http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/P51605 P51605] ZINC has 1671385 entry, and the ring in it does not show as aromatic.<br />
<br />
<br />
[[Category:Errata]]<br />
[[Category:ZINC]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Docking_programs&diff=1441Docking programs2007-12-06T19:58:58Z<p>JohnIrwin: </p>
<hr />
<div>Other docking programs (besides DOCK).<br />
<br />
<br />
* Taylor P, Blackburn E, Sheng YG, Harding S, Hsin KY, Kan D, Shave S, Walkinshaw MD., Abstract Ligand discovery and virtual screening using the program LIDAEUS., Br J Pharmacol. 2007 Nov 26; <br />
<br />
* <br />
<br />
[[Category:Literature]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Greatest_hits&diff=2893Greatest hits2007-12-06T19:57:40Z<p>JohnIrwin: </p>
<hr />
<div>This is a page about docking successes. I am just going to paste papers in here, with a view to creating a table and maybe a review article some day.<br />
<br />
* Dhagat U, Carbone V, Chung RP, Matsunaga T, Endo S, Hara A, El-Kabbani O., A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase, Med Chem. 2007 Nov;3(6):546-50. <br />
<br />
* Feder M, Purta E, Koscinski L, Cubrilo S, Maravic Vlahovicek G, Bujnicki JM., Virtual Screening and Experimental Verification to Identify Potential Inhibitors of the ErmC Methyltransferase Responsible for Bacterial Resistance against Macrolide Antibiotics.,ChemMedChem. 2007 Nov 23;<br />
<br />
[[Category:Literature]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1135DUD:Errata2007-12-06T19:53:18Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
* In the DUD paper, J Med Chem 2006, Huang, Shoichet, Irwin, jm0608356. The PDB id of ADA in table1 is wrong. It should be "1ndw", not "1stw". Our final version submitted was correct, but we failed to catch this in the galleys. <br />
<br />
* Q: Why is the ratio of decoys to annotated ligands described as 36 to 1 in the paper, yet there are on average only 33 to 1 in DUD? This is due to overlap, as the same decoy could be used for multiple targets, particularly in the kinase class where there was so much overlap.<br />
<br />
* Two DUD decoy compounds (ZINC154632 for RXR decoys and ZINC608655 for ER decoys) were structurally identical/similar to the crystal ligands of RXR and ER, individually. This problem was caused by failing to include the crystallographic ligands in our annotated ligands set, and will be fixed in the next version of DUD. Thanks to Paul Hawkins of OpenEye for bringing this to our attention.<br />
<br />
* Also: PDB code for COX-1 structure in given as 1P4G but should be 1Q4G. We regret this error, and thank alert reader Paul Hawkins of OpenEye for this information Also, Hao Li of UCSF Pharm Chem points out that the PDB id of ADA in the paper is wrong. It should be 1ndw. <br />
<br />
= Factor Xa =<br />
* These each have amidine groups that have been over-protonated so that<br />
the amidine is no longer a planar Nsp2-Csp2-Nsp2 structure: ZINC03831927, 04629420, 04633281<br />
<br />
* This ligand has a piperazine group that is doubly protonated. In vivo<br />
either single protonation or (possibly) no protonation at all would be<br />
the norm. I don't believe the alternative structures are in the active set: ZINC03815578<br />
<br />
* These structures all have suspicious protonated dihydropyridine<br />
structures. Such an unstable substructure is most unlikely to be present<br />
in a stable Factor Xa ligand as it would very rapidly oxidatively<br />
aromatise to the protonated pyridine. Therefore I suspect that these<br />
substructures are all incorrect: ZINC03815848, 3814850, 4631018, 4631023, 4631034<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1134DUD:Errata2007-12-06T19:50:16Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
* In the DUD paper, J Med Chem 2006, Huang, Shoichet, Irwin, jm0608356. The PDB id of ADA in table1 is wrong. It should be "1ndw", not "1stw". Our final version submitted was correct, but we failed to catch this in the galleys. <br />
<br />
* Q: Why is the ratio of decoys to annotated ligands described as 36 to 1 in the paper, yet there are on average only 33 to 1 in DUD? This is due to overlap, as the same decoy could be used for multiple targets, particularly in the kinase class where there was so much overlap.<br />
<br />
* Two DUD decoy compounds (ZINC154632 for RXR decoys and ZINC608655 for ER decoys) were structurally identical/similar to the crystal ligands of RXR and ER, individually. This problem was caused by failing to include the crystallographic ligands in our annotated ligands set, and will be fixed in the next version of DUD. Thanks to Paul Hawkins of OpenEye for bringing this to our attention.<br />
<br />
* Also: PDB code for COX-1 structure in given as 1P4G but should be 1Q4G. We regret this error, and thank alert reader Paul Hawkins of OpenEye for this information Also, Hao Li of UCSF Pharm Chem points out that the PDB id of ADA in the paper is wrong. It should be 1ndw. <br />
<br />
= Factor Xa =<br />
* These each have amidine groups that have been over-protonated so that<br />
the amidine is no longer a planar Nsp2-Csp2-Nsp2 structure<br />
ZINC03831927, 04629420, 04633281<br />
<br />
* This ligand has a piperazine group that is doubly protonated. In vivo<br />
either single protonation or (possibly) no protonation at all would be<br />
the norm. I don't believe the alternative structures are in the active set: ZINC03815578<br />
<br />
* These structures all have suspicious protonated dihydropyridine<br />
structures. Such an unstable substructure is most unlikely to be present<br />
in a stable Factor Xa ligand as it would very rapidly oxidatively<br />
aromatise to the protonated pyridine. Therefore I suspect that these<br />
substructures are all incorrect: ZINC03815848, 3814850, 4631018, 4631023, 4631034<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1133DUD:Errata2007-12-06T18:54:00Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
= Paper =<br />
<br />
* In the DUD paper, J Med Chem 2006, Huang, Shoichet, Irwin, jm0608356. The PDB id of ADA in table1 is wrong. It should be "1ndw", not "1stw". Our final version submitted was correct, but we failed to catch this in the galleys. <br />
<br />
* Q: Why is the ratio of decoys to annotated ligands described as 36 to 1 in the paper, yet there are on average only 33 to 1 in DUD? This is due to overlap, as the same decoy could be used for multiple targets, particularly in the kinase class where there was so much overlap.<br />
<br />
* Two DUD decoy compounds (ZINC154632 for RXR decoys and ZINC608655 for ER decoys) were structurally identical/similar to the crystal ligands of RXR and ER, individually. This problem was caused by failing to include the crystallographic ligands in our annotated ligands set, and will be fixed in the next version of DUD. Thanks to Paul Hawkins of OpenEye for bringing this to our attention.<br />
<br />
* Also: PDB code for COX-1 structure in given as 1P4G but should be 1Q4G. We regret this error, and thank alert reader Paul Hawkins of OpenEye for this information Also, Hao Li of UCSF Pharm Chem points out that the PDB id of ADA in the paper is wrong. It should be 1ndw. <br />
<br />
<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1132DUD:Errata2007-12-06T18:24:59Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
= Paper =<br />
<br />
* In the DUD paper, J Med Chem 2006, Huang, Shoichet, Irwin, jm0608356. The PDB id of ADA in table1 is wrong. It should be "1ndw", not "1stw". Our final version submitted was correct, but we failed to catch this in the galleys. <br />
* There are more<br />
<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DUD:Errata&diff=1131DUD:Errata2007-12-06T01:48:06Z<p>JohnIrwin: </p>
<hr />
<div>DUD Errata<br />
<br />
<br />
[[Category:DUD]]<br />
[[Category:Errata]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Catalyst&diff=273Catalyst2007-12-05T23:46:20Z<p>JohnIrwin: </p>
<hr />
<div>This is about the perl package Catalyst. For information about catalysts as agents that lower the activation energy of a chemical reaction, see your chemistry or biophysics textbook.<br />
<br />
= Installation = <br />
perl -MCPAN -e shell<br />
>> install Catalyst::Runtime<br />
(hit return to take all defaults)<br />
(implies installation of around 100 dependencies)<br />
(may require fresh installation of Bundle::CPAN)<br />
(correctly configured version running on bks150)<br />
<br />
>> install Task::Catalyst<br />
(takes about an hour!)<br />
<br />
= Getting started =<br />
<br />
mkdir winc<br />
cd winc<br />
catalyst.pl create winc<br />
<br />
= Advice and notes = <br />
<br />
<br />
[[Category:Internal]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Catalyst&diff=272Catalyst2007-12-05T21:48:34Z<p>JohnIrwin: </p>
<hr />
<div>This is about the perl package Catalyst. For information about catalysts as agents that lower the activation energy of a chemical reaction, see your chemistry or biophysics textbook.<br />
<br />
= Installation = <br />
perl -MCPAN -e shell<br />
>> install Catalyst::Runtime<br />
(hit return to take all defaults)<br />
(implies installation of around 100 dependencies)<br />
(may require fresh installation of Bundle::CPAN)<br />
(correctly configured version running on bks150)<br />
<br />
= Getting started =<br />
<br />
<br />
<br />
<br />
= Advice and notes = <br />
<br />
<br />
[[Category:Internal]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Applications_of_DOCK&diff=114Applications of DOCK2007-12-05T18:06:56Z<p>JohnIrwin: </p>
<hr />
<div><br />
<br />
= Use DOCK to identify binding site. =<br />
<br />
Please see the paper:<br />
Zhong, S.; MacKerell, A. D., Jr.<br />
Binding Response: A Descriptor for Selecting Ligand Binding Site on Protein Surfaces<br />
J. Chem. Inf. Model; (Article); 2007; 47(6); 2303-2315.<br />
Hope it will be helpful for solving your problem.<br />
<br />
<br />
[[Category:References]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorial_6&diff=1051DOCK Blaster:Tutorial 62007-12-04T04:26:16Z<p>JohnIrwin: </p>
<hr />
<div>This is one of the [[DOCK Blaster:Tutorials]].<br />
<br />
<br />
Multiple crystal structures available.<br />
<br />
<br />
This tutorial is not yet ready.</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorial_5&diff=1046DOCK Blaster:Tutorial 52007-12-04T04:25:46Z<p>JohnIrwin: </p>
<hr />
<div>This is one of the [[DOCK Blaster:Tutorials]].<br />
<br />
No crystal structure available.<br />
<br />
This article is not yet ready.</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorial_4&diff=1041DOCK Blaster:Tutorial 42007-12-04T04:25:16Z<p>JohnIrwin: </p>
<hr />
<div>This is one of the [[DOCK Blaster:Tutorials]].<br />
<br />
Only apo structure available.<br />
<br />
This article is not yet ready.</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorial_3&diff=1036DOCK Blaster:Tutorial 32007-12-04T04:24:41Z<p>JohnIrwin: </p>
<hr />
<div>This is one of the [[DOCK Blaster:Tutorials]].<br />
<br />
This article is not yet ready.</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorial_2&diff=1031DOCK Blaster:Tutorial 22007-12-04T04:23:52Z<p>JohnIrwin: </p>
<hr />
<div>'''DOCK Blaster Tutorial 1. Docking Methotrexate (MTX) to Dhihydrofolate Reductase (DHFR)''' A[[DOCK Blaster:Tutorials | DOCK Blaster Tutorial]].<br />
{{TOCright}}<br />
[[Image:1dfr.jpg|thumb|right|Mineralocorticoid receptor, PDB 1drf]]<br />
<br />
= Specific Aims =<br />
This tutorial will show you how to retrospectively dock a crystallographically observed ligand, aldosterone, into the human mineralocorticoid receptor, PDB code <br />
[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2AA2 2aa2]. You will also dock a list of annotated actives from the literature, as well as property-matched decoys. Finally, you will prospectively dock the ZINC "fragment-like" library into MR, and pick compounds to test as possible binders. The questions are:<br />
<br />
* 1. Can DOCK Blaster re-dock the native ligand close to its crystallographically observed position, with a competitive score?<br />
* 2. Can DOCK Blaster enrich known actives from a database of property-matched decoys?<br />
* 3. Can DOCK Blaster suggest novel, commercially available ligands for MR?<br />
<br />
[[Image:Mtx.png|thumb|right|Methotrexate, the crystallographically observed ligand of DHFR in 3dfr]]<br />
<br />
= Background and Significance =<br />
Methotrexate (MTX) binds to dihydrofolate reductase (DHFR) with high affinity, and has thus been used in chemotherapy for many years. DHFR reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. Because tetrahydrofolate, the product of this reaction, is the active form of folate in humans, inhibition of DHFR can cause functional folate deficiency. Because folate is needed by rapidly dividing cells to make thymine, this effect may be therapeutic.<br />
<br />
<br />
= Preliminary Results = <br />
We will attempt to use DOCK Blaster to answer these questions, using data that has been prepared in advance. If you wish to use DOCK Blaster on your own project, you must prepare the data yourself. See [[DOCK Blaster:Input Preparation | Input Preparation]] for details.<br />
<br />
== Protocol 1 - Prepare input files ==<br />
* P1.1. Go to the benchmarking data page [http://data.docking.org/ data.docking.org] and browse the DUD40 set, selecting the [http://data.docking.org/dud40/mr/ MR set]. Download each of these five files. On windows, you do this by right mouse clicking and selecting "save link as". If you are using your own target, you must prepare the files yourself (see [[DOCK Blaster:Input Preparation | Input Preparation]]).<br />
<br />
[[Image:DBtut1_1f.jpg|thumb|right|Figure T1.1 - Prepare input and launch job]]<br />
<br />
== Protocol 2 - Submit job and review results ==<br />
* P2.1. Go to the [http://blaster.docking.org | DOCK Blaster main page] and select [http://blaster.docking.org/start.shtml | Queue A Job] from the DOCK! pull down menu (Figure T1.1). Fill in the form as in the figure, as follows. <br />
** a. In the "Target" field, select the receptor, rec.pdb. <br />
** b. In the next field, select "Docked ligand" and select the ligand, xtal-lig.mol2. <br />
** c. In the "Actives" field, select the actives.smi file.<br />
** d. In the "Inactives" field, select the inactives.smi file.<br />
** e. In "Email for reports", enter your email address (optional).<br />
** f. In the "Aim of this experiment" field, write a short memo about what you are doing.<br />
** g. Check your input, and click "DOCK!" when you are ready. <br />
<br />
If you have followed the steps above, your screen should now look something like Figure Tut1-1 (right).<br />
[[Image:DBtut1_2f.jpg|thumb|right|Figure T1.2 - Scrutinizer - data are uploaded, checked, and the job is started]].<br />
<br />
* P2.2. Depending on available system resources, your job is now either running, or queued to run when a slot becomes available. If your screen does not look like Figure T1.2, check the input and try again. If the job is still failing after the third attempt, please write to support at docking.org for assistance.<br />
<br />
* P2.3. Read what is reported by the Scrutinizer (Figure T1.2), and proceed to the Job Watcher by clicking on the link at the bottom of the page when you are ready.<br />
<br />
* P2.4. You should now be in the Job Watcher (Figure T1.3). Depending on how much time has elapsed, and how busy our cluster is, you will see a progress report of the current status of your job. As time passes, the yellow status indicator should progress from left to right indicating the progress of your job through Target Preparation and Calibration. <br />
<br />
* P2.5. If all goes as usual, your job will have completed within an hour. You may reload the Job Watcher at any time to get an updated status report of your job. When calibration is complete, you may review the preliminary results and decide on the next course of action. <br />
<br />
* P2.6 Review Calibration results. blah blah blah.<br />
[[Image:DBtut1_3f.jpg|thumb|right|Figure T1.3]]<br />
<br />
<br />
<br />
<br />
= Proposed Research = <br />
Preliminary results above show that docking is able to enrich known actives from among a database of decoys. This suggests that prospective docking for discovery of novel ligands is reasonable and can be expected to suggest interesting compounds to test. <br />
<br />
== Protocol 3. Dock purchasable fragments ==<br />
<br />
== Protocol 4. Review and interpret docking == <br />
<br />
== Protocol 5. Prioritize for testing ==<br />
<br />
== Protocol 6. Suggested variations ==<br />
<br />
== Possible problems & other approaches ==<br />
<br />
[[Image:DBtut1_4f.jpg|thumb|right|Figure T1.4]]<br />
<br />
= Literature Cited = <br />
We refer you to our publications pages for theory and practice of docking and virtual screening. <br />
* [[Publications:DOCK]]<br />
* [[Publications:ZINC]]<br />
* [[Publications:DUD]]<br />
* [[Publications:Reviews_and_opinion]]<br />
* [[Publications:Targets]]<br />
<br />
Document status: working tutorial. Please correct any errors you may find.<br />
<br />
[[Category:DOCK Blaster]]<br />
[[Category:Tutorials]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
{{TOCright}}<br />
'''DOCK Blaster Tutorial 1. Docking Methotrexate (MTX) to Dhihydrofolate Reductase (DHFR)'''<br />
<br />
This is one of the [[DOCK Blaster:Tutorials]].<br />
== Conceptual Overview ==<br />
Methotrexate (MTX, depicted) binds to human dihydrofolate reductase (DHFR) with high affinity, and has been used in clinical oncology for over 20 years. A crystal structure is available (PDB code 3dfr, depicted) with MTX in the binding site.<br />
* Question 1. Is DOCK Blaster able to suggest other compounds from a commercially available library that might be active against dihydrofolate reductase?<br />
** Sub-question 1.1. Is DOCK Blaster able to re-dock MTX close to its crystallographically observed position, with a competitive score?<br />
** Sub-question 1.2. Is DOCK Blaster able to enrich MTX compared with 50 property-matched decoys, compounds with similar properties to MTX but dissimilar topology?<br />
** Sub-question 1.3. Is DOCK Blaster able to enrich known actives, and de-enrich known inactives, against DHFR?<br />
<br />
picture of MTX<br />
<br />
picture of 3dfr<br />
<br />
picture of MTX bound to 3dfr<br />
<br />
picture of other DHFR ligands<br />
<br />
== From Theory to Action ==<br />
We will attempt to use DOCK Blaster to answer these questions, using data that has been prepared in advance. If you wish to use DOCK Blaster on your own project, you must prepare data to conform with [[DOCK Blaster:Input Preparation | DOCK Blaster's]] basic requirements. To do this tutorial, please carefully follow the steps below. This tutorial usually takes about two hours, but most of the time is simply waiting for the computers to do the work on our servers.<br />
<br />
== Literature References ==<br />
McMaster study<br />
Blaney's Magnum opus. <br />
<br />
<br />
== Collecting and formatting relevant data ==<br />
<br />
<br />
== Launch Preliminary Calculation ==<br />
** 1. Go to DOCK Blaster web page [http://blaster.docking.org blaster.docking.org]. Please note that during pre-alpha testing this page is different. Contact [[John Irwin]] for details. <br />
** 2. Click on "Start docking!" to go to the input preparation page.<br />
** 3. Click on "HELP" to open up the documentation for input preparation in a separate window. <br />
*** 3.1. In the documentation window, click on "Sample Data" at the end of the first paragraph. <br />
*** 3.2 In the sample data window, click on the link to data.docking.org<br />
*** 3.3. Click on DUD40.<br />
*** 3.4. Click on CDK2.<br />
*** 3.5. Right mouse to save all five files in this directory on your disk. <br />
*** 3.6. Close the documentation window, returning to the DOCK Blaster input form.<br />
** 4. Click on the first "Browse" button (to the right of Target) and select the rec.pdb file you just downloaded. <br />
** 5. In the next field "docked ligand" select the xtal-lig.mol2 file.<br />
** 6. Optionally, you may select the actives.smi and inactives.smi from the next two lines. <br />
** 7. Enter your email address if you wish to receive progress reports by email.<br />
** 8. Enter a brief comment about the calculation. <br />
** 9. (optional: enter cofactor.par below)<br />
<br />
If you have followed the steps above, your screen should now look something like Figure Tut1-1 (right).<br />
[[Image:Tut1-1.jpg|thumb|right|Figure Tut1-1]]<br />
<br />
** 10. Click on "DOCK" to upload the files and begin docking. You will be taken to the "Submission Scrutinizer", as depicted in Figure Tut1-2. <br />
[[Image:Tut1-2.jpg|thumb|right|Figure Tut1-2]] <br />
<br />
** 11. Your job should now be running. If it is not, there is either some part of the above instructions you did not follow, or we are currently experiencing problems with our systems.<br />
<br />
** 12. Read through the submission scrutinizer, and go to the Job Watcher by clicking on the link at the bottom of the page... http://blaster.docking.org/cgi-bin/jobmon.pl<br />
<br />
** 13. You should now be in the Job Watcher. Depending on how much time has elapsed, and how busy our cluster is, you will see a progress report of your job. It might look something like Figure Tut1-3. [[Image:Tut1-3.jpg|thumb|right|Figure Tut1-3]]<br />
<br />
** 14. If all goes well, the job will complete in about an hour. You may reload the page at anytime to get updated status of the job progress. <br />
<br />
** 15. Preliminary docking normally begins after the site preparation is complete, often about 15 minutes after you first submitted the job. Once preliminary docking results are available, new links appear in the job watcher to allow you to start to see docked ligands. Caution: until the preliminary docking is complete, it can be misleading to rely upon incomplete preliminary docking results to reach any conclusions about the docking results.<br />
<br />
== Examining the Results ==<br />
<br />
== Docking a Database ==<br />
<br />
== Browsing and interpreting the results == <br />
<br />
== Follow up and variations ==<br />
<br />
== Possible problems and alternative approaches ==<br />
<br />
<br />
[[Category:DOCK Blaster]]<br />
[[Category:Tutorials]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorials&diff=1087DOCK Blaster:Tutorials2007-12-03T21:16:54Z<p>JohnIrwin: </p>
<hr />
<div>'''Introduction'''<br />
{{TOCright}}<br />
These tutorials are designed to illustrate the use of DOCK Blaster using real-world examples, with data drawn from and referenced back to the chemical and biological literature. We recommend you complete at least one tutorial before trying with your own data. If you have to pick only one, we suggest you choose the tutorial that most closely resembles your own research situation. Each of these tutorials should provide a useful first time experience for a beginner. Each is targeted at a particular kind of docking scenario, some of which are further discussed in the [[DOCK Blaster:Preliminaries | preliminary considerations]] article.<br />
<br />
Tutorials are organized like a grant, which we hope you find helpful. (If not, let us know!).<br />
<br />
= [[DOCK Blaster:Tutorial 1 | Dock to minearalocorticoid receptor (MR)]] =<br />
A [[nuclear hormone receptor]], drawn from [[DUD]], that illustrates the use of DOCK Blaster when both actives and inactive controls are available. <br />
<br />
= [[DOCK Blaster:Tutorial 2 | Dock methotrexate (MTX) to dihydrofolate reductase (DHFR)]] =<br />
This is a classic case from the history of molecular docking, also from [[DUD]] with an extensive literature. It serves to illustrate the use of a co-factor bound to the target.<br />
<br />
= [[DOCK Blaster:Tutorial 3 | Dock to angiotensin II converting enzyme (ACE)]] =<br />
This case, also from [[DUD]], illustrates the use of DOCK Blaster on zinc metalloenzymes.<br />
<br />
= [[DOCK Blaster:Tutorial 4 | Only apo structure available]] =<br />
DOCK to cruzain, a cystein protease target for Chagas' Disease, for which only an apo structure is available.<br />
Describes both modeling a ligand in, and using protein residues in the binding site to indicate the binding site. Lack of diagnostics because of no available ligand.<br />
<br />
= [[DOCK Blaster:Tutorial 5 | No crystal structure available]] =<br />
DOCK to a target for which no crystal structure is available.<br />
Describes the use of Blast/Modbase to obtain and evaluate a structure.<br />
Describes checking the model of the target for suitability for docking.<br />
<br />
= [[DOCK Blaster:Tutorial 6 | Multiple crystal structures available]] =<br />
Multiple crystal structures available. <br />
Multiple actives and inactives available.<br />
How to optimise the use of DOCK Blaster for this case.<br />
<br />
You are welcome to write new tutorials - this IS a wiki! You are also welcome to suggest new tutorials, to support at docking.org.<br />
<br />
[[Category:DOCK Blaster]]<br />
[[Category:Tutorials]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorials&diff=1086DOCK Blaster:Tutorials2007-12-03T21:16:20Z<p>JohnIrwin: </p>
<hr />
<div>'''Introduction'''<br />
{{TOCright}}<br />
These tutorials are designed to illustrate the use of DOCK Blaster using real-world examples, with data drawn from and referenced back to the chemical and biological literature. We recommending completing at least one tutorial before trying with your own data. If you have to pick only one, we suggest you choose the tutorial that most closely resembles your own research situation. Each of these tutorials should provide a useful first time experience for a beginner. Each is targeted at a particular kind of docking scenario, some of which are further discussed in the [[DOCK Blaster:Preliminaries | preliminary considerations]] article.<br />
<br />
Tutorials are organized like a grant, which we hope you find helpful. (If not, let us know!).<br />
<br />
= [[DOCK Blaster:Tutorial 1 | Dock to minearalocorticoid receptor (MR)]] =<br />
A [[nuclear hormone receptor]], drawn from [[DUD]], that illustrates the use of DOCK Blaster when both actives and inactive controls are available. <br />
<br />
= [[DOCK Blaster:Tutorial 2 | Dock methotrexate (MTX) to dihydrofolate reductase (DHFR)]] =<br />
This is a classic case from the history of molecular docking, also from [[DUD]] with an extensive literature. It serves to illustrate the use of a co-factor bound to the target.<br />
<br />
= [[DOCK Blaster:Tutorial 3 | Dock to angiotensin II converting enzyme (ACE)]] =<br />
This case, also from [[DUD]], illustrates the use of DOCK Blaster on zinc metalloenzymes.<br />
<br />
= [[DOCK Blaster:Tutorial 4 | Only apo structure available]] =<br />
DOCK to cruzain, a cystein protease target for Chagas' Disease, for which only an apo structure is available.<br />
Describes both modeling a ligand in, and using protein residues in the binding site to indicate the binding site. Lack of diagnostics because of no available ligand.<br />
<br />
= [[DOCK Blaster:Tutorial 5 | No crystal structure available]] =<br />
DOCK to a target for which no crystal structure is available.<br />
Describes the use of Blast/Modbase to obtain and evaluate a structure.<br />
Describes checking the model of the target for suitability for docking.<br />
<br />
= [[DOCK Blaster:Tutorial 6 | Multiple crystal structures available]] =<br />
Multiple crystal structures available. <br />
Multiple actives and inactives available.<br />
How to optimise the use of DOCK Blaster for this case.<br />
<br />
You are welcome to write new tutorials - this IS a wiki! You are also welcome to suggest new tutorials, to support at docking.org.<br />
<br />
[[Category:DOCK Blaster]]<br />
[[Category:Tutorials]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorials&diff=1085DOCK Blaster:Tutorials2007-12-03T21:15:58Z<p>JohnIrwin: </p>
<hr />
<div>'''Introduction to Tutorials'''<br />
{{TOCright}}<br />
These tutorials are designed to illustrate the use of DOCK Blaster using real-world examples, with data drawn from and referenced back to the chemical and biological literature. We recommending completing at least one tutorial before trying with your own data. If you have to pick only one, we suggest you choose the tutorial that most closely resembles your own research situation. Each of these tutorials should provide a useful first time experience for a beginner. Each is targeted at a particular kind of docking scenario, some of which are further discussed in the [[DOCK Blaster:Preliminaries | preliminary considerations]] article.<br />
<br />
Tutorials are organized like a grant, which we hope you find helpful. (If not, let us know!).<br />
<br />
= [[DOCK Blaster:Tutorial 1 | Dock to minearalocorticoid receptor (MR)]] =<br />
A [[nuclear hormone receptor]], drawn from [[DUD]], that illustrates the use of DOCK Blaster when both actives and inactive controls are available. <br />
<br />
= [[DOCK Blaster:Tutorial 2 | Dock methotrexate (MTX) to dihydrofolate reductase (DHFR)]] =<br />
This is a classic case from the history of molecular docking, also from [[DUD]] with an extensive literature. It serves to illustrate the use of a co-factor bound to the target.<br />
<br />
= [[DOCK Blaster:Tutorial 3 | Dock to angiotensin II converting enzyme (ACE)]] =<br />
This case, also from [[DUD]], illustrates the use of DOCK Blaster on zinc metalloenzymes.<br />
<br />
= [[DOCK Blaster:Tutorial 4 | Only apo structure available]] =<br />
DOCK to cruzain, a cystein protease target for Chagas' Disease, for which only an apo structure is available.<br />
Describes both modeling a ligand in, and using protein residues in the binding site to indicate the binding site. Lack of diagnostics because of no available ligand.<br />
<br />
= [[DOCK Blaster:Tutorial 5 | No crystal structure available]] =<br />
DOCK to a target for which no crystal structure is available.<br />
Describes the use of Blast/Modbase to obtain and evaluate a structure.<br />
Describes checking the model of the target for suitability for docking.<br />
<br />
= [[DOCK Blaster:Tutorial 6 | Multiple crystal structures available]] =<br />
Multiple crystal structures available. <br />
Multiple actives and inactives available.<br />
How to optimise the use of DOCK Blaster for this case.<br />
<br />
You are welcome to write new tutorials - this IS a wiki! You are also welcome to suggest new tutorials, to support at docking.org.<br />
<br />
[[Category:DOCK Blaster]]<br />
[[Category:Tutorials]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorials&diff=1084DOCK Blaster:Tutorials2007-12-03T21:15:40Z<p>JohnIrwin: </p>
<hr />
<div>'''Introduction to Tutorials'''<br />
{{TOCright}}<br />
These tutorials are designed to illustrate the use of DOCK Blaster using real-world examples, with data drawn from and referenced back to the chemical and biological literature. We recommending completing at least one tutorial before trying with your own data. If you have to pick only one, we suggest you choose the tutorial that most closely resembles your own research situation. Each of these tutorials should provide a useful first time experience for a beginner. Each is targeted at a particular kind of docking scenario, some of which are further discussed in the [[DOCK Blaster:Preliminaries preliminary considerations]] article.<br />
<br />
Tutorials are organized like a grant, which we hope you find helpful. (If not, let us know!).<br />
<br />
= [[DOCK Blaster:Tutorial 1 | Dock to minearalocorticoid receptor (MR)]] =<br />
A [[nuclear hormone receptor]], drawn from [[DUD]], that illustrates the use of DOCK Blaster when both actives and inactive controls are available. <br />
<br />
= [[DOCK Blaster:Tutorial 2 | Dock methotrexate (MTX) to dihydrofolate reductase (DHFR)]] =<br />
This is a classic case from the history of molecular docking, also from [[DUD]] with an extensive literature. It serves to illustrate the use of a co-factor bound to the target.<br />
<br />
= [[DOCK Blaster:Tutorial 3 | Dock to angiotensin II converting enzyme (ACE)]] =<br />
This case, also from [[DUD]], illustrates the use of DOCK Blaster on zinc metalloenzymes.<br />
<br />
= [[DOCK Blaster:Tutorial 4 | Only apo structure available]] =<br />
DOCK to cruzain, a cystein protease target for Chagas' Disease, for which only an apo structure is available.<br />
Describes both modeling a ligand in, and using protein residues in the binding site to indicate the binding site. Lack of diagnostics because of no available ligand.<br />
<br />
= [[DOCK Blaster:Tutorial 5 | No crystal structure available]] =<br />
DOCK to a target for which no crystal structure is available.<br />
Describes the use of Blast/Modbase to obtain and evaluate a structure.<br />
Describes checking the model of the target for suitability for docking.<br />
<br />
= [[DOCK Blaster:Tutorial 6 | Multiple crystal structures available]] =<br />
Multiple crystal structures available. <br />
Multiple actives and inactives available.<br />
How to optimise the use of DOCK Blaster for this case.<br />
<br />
You are welcome to write new tutorials - this IS a wiki! You are also welcome to suggest new tutorials, to support at docking.org.<br />
<br />
[[Category:DOCK Blaster]]<br />
[[Category:Tutorials]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=XML_RPC_Services&diff=4717XML RPC Services2007-12-01T06:36:52Z<p>JohnIrwin: </p>
<hr />
<div>We offer several XML RPC (XMLRPC) services. These are based on supported [[XML RPC Procedures]]. This page is a crib sheet on how to use these services. Note that the use of docking.org services may be subject to quotas. see [http://www.xmlrpc.com/ http://www.xmlrpc.com/]<br />
<br />
* Step 1. Download the client<br />
** Client [http://blaster.docking.org/xmlrpc/xmlclient.py xmlclient.py]<br />
* Step 2. Download the sample data<br />
** Sample data ZIP file [http://blaster.docking.org/data/dud40.zip dud40.zip]<br />
** Browse [http://blaster.docking.org/data/dud40/ sample data]<br />
** unzip dud40.zip<br />
* Step 3. Protonate AChE receptor PDB file<br />
** xmlclient.py protonate_united ache ; expects rec.pdb ; returns newrec.pdb <br />
*** ; this takes rec.pdb and returns newrec.pdb, with united atoms protonated<br />
* Step 4. Run DOCK Blaster<br />
** xmlclient.py dock ache ; returns DOCK Blaster Job ID number<br />
** browse results [http://blaster.docking.org/cgi-bin/jobwatch.pl?job_id=993&pin= | results]<br />
* Step 5. Upload data and process ligands in ZINC<br />
** xmlclient.py upload actives.smi ; returns ZINC upload number<br />
* Step 6. Search ZINC using SMILES<br />
** xmlclient.py match_smiles test1.smi; returns list<br />
* Step 7. Search ZINC using SMARTS<br />
** xmlclient.py match_smarts test2.sma; returns list<br />
* Step 8. Find similars in ZINC<br />
** xmlclient.py getsimilars actives.smi; returns list<br />
* Step 9. Find decoys in ZINC<br />
** xmlclient.py getdecoys actives.smi; returns list<br />
* Step 10. blah<br />
** xmlclient.py blah blah<br />
* Step 11. blah<br />
** xmlclient.py blah blah<br />
* Step 12. blah<br />
** xmlclient.py blah blah<br />
* Step 13. blah<br />
** xmlclient.py blah blah</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Docking_for_non-experts&diff=1437Docking for non-experts2007-11-30T23:50:33Z<p>JohnIrwin: </p>
<hr />
<div>Docking for non-experts aims to be an easy to follow and use guide for non-specialists wishing to computational target-based ligand discovery (docking, virtual screening) techniques. <br />
<br />
Table of Contents<br />
<br />
= Framing the problem =<br />
<br />
= Available software = <br />
<br />
= Protocols = <br />
<br />
= FAQ = <br />
<br />
= Pitfalls = <br />
<br />
<br />
[[Category:How-to guides]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Docking_for_experts&diff=1435Docking for experts2007-11-30T23:48:08Z<p>JohnIrwin: </p>
<hr />
<div>This is the docking for experts main page. The goal of "docking for experts" is to be a comprehensive resource of everything an expert docker needs to know in order to perform the best target-based computational ligand discovery possible.<br />
<br />
Table of Contents<br />
<br />
= Background Information = <br />
<br />
= Problems = <br />
* receptor flexibility<br />
* scoring function<br />
<br />
= Software =<br />
== Docking software ==<br />
<br />
== Ligand handling software ==<br />
<br />
== Chemical informatics software ==<br />
<br />
== Important papers ==<br />
<br />
<br />
= Databases = <br />
<br />
<br />
[[Category:How to guides]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Asthma&diff=120Asthma2007-11-30T21:39:56Z<p>JohnIrwin: </p>
<hr />
<div>Therapeutic targets for Asthma.<br />
<br />
= Structure available = <br />
<br />
<br />
= Good homology model available = <br />
<br />
<br />
= No target structure available = <br />
<br />
= Unknown = <br />
<br />
<br />
<br />
* acidic mammalian chitinase (AMCase) <br />
[http://www.sciencedaily.com/releases/2004/06/040614080309.htm ref]<br />
<br />
* Interleukin-5 and eosinophils <br />
[http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W7J-45F4VBK-R&_user=4430&_coverDate=04%2F01%2F2002&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000059594&_version=1&_urlVersion=0&_userid=4430&md5=66378c9b33b6955bdc6e576416d5edd8 ref]<br />
<br />
* adenosine receptors <br />
[http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=14720064 ref]<br />
<br />
* Calcium sensors <br />
[http://www.fasebj.org/cgi/content/abstract/01-0018fjev1 ref]<br />
<br />
* Immunoglobulin E (IgE)<br />
[http://pharmalicensing.com/articles/disp/936280162_37ce8062e496e ref]<br />
<br />
* interleukin-9 <br />
[http://www.ingentaconnect.com/content/apl/ett/1999/00000003/00000001/art00003 ref]<br />
<br />
* Eotaxin and CCR3 <br />
[http://www.pasteur.fr/applications/euroconf/chemokines2/Williams.pdf ref]<br />
<br />
* Interleukin-4 and Interleukin-13 <br />
[http://webmedbooks.com/osucom/content/productdetail.aspx/upc=0299c432-f124-405c-99b0-5015ffc4e21e/ ref]<br />
<br />
* Toll-like receptors<br />
[http://www.nature.com/nrd/journal/v1/n10/full/nrd914.html ref]<br />
<br />
* US patents, 2000-2004 (from Zheng, Pharmaceutical Sci. 2006<br />
<br />
{alpha}2-Adrenergic receptor<br />
beta-Adrenergic receptor<br />
Substance P receptor (39)<br />
Cyclooxygenase 2 (38)<br />
Adenosine A1 receptor <br />
Adenosine A2b receptor <br />
Endothelin A receptor <br />
Endothelin B receptor<br />
5-Lipoxygenase (8)<br />
Serine protease (7)<br />
IL-1R-a<br />
<br />
<br />
[[Category:Targets]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Asthma&diff=119Asthma2007-11-30T21:38:26Z<p>JohnIrwin: </p>
<hr />
<div>Therapeutic targets for Asthma<br />
<br />
* acidic mammalian chitinase (AMCase) <br />
[http://www.sciencedaily.com/releases/2004/06/040614080309.htm ref]<br />
<br />
* Interleukin-5 and eosinophils <br />
[http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W7J-45F4VBK-R&_user=4430&_coverDate=04%2F01%2F2002&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000059594&_version=1&_urlVersion=0&_userid=4430&md5=66378c9b33b6955bdc6e576416d5edd8 ref]<br />
<br />
* adenosine receptors <br />
[http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=14720064 ref]<br />
<br />
* Calcium sensors <br />
[http://www.fasebj.org/cgi/content/abstract/01-0018fjev1 ref]<br />
<br />
* Immunoglobulin E (IgE)<br />
[http://pharmalicensing.com/articles/disp/936280162_37ce8062e496e ref]<br />
<br />
* interleukin-9 <br />
[http://www.ingentaconnect.com/content/apl/ett/1999/00000003/00000001/art00003 ref]<br />
<br />
* Eotaxin and CCR3 <br />
[http://www.pasteur.fr/applications/euroconf/chemokines2/Williams.pdf ref]<br />
<br />
* Interleukin-4 and Interleukin-13 <br />
[http://webmedbooks.com/osucom/content/productdetail.aspx/upc=0299c432-f124-405c-99b0-5015ffc4e21e/ ref]<br />
<br />
* Toll-like receptors<br />
[http://www.nature.com/nrd/journal/v1/n10/full/nrd914.html ref]<br />
<br />
* US patents, 2000-2004 (from Zheng, Pharmaceutical Sci. 2006<br />
<br />
{alpha}2-Adrenergic receptor<br />
beta-Adrenergic receptor<br />
Substance P receptor (39)<br />
Cyclooxygenase 2 (38)<br />
Adenosine A1 receptor <br />
Adenosine A2b receptor <br />
Endothelin A receptor <br />
Endothelin B receptor<br />
5-Lipoxygenase (8)<br />
Serine protease (7)<br />
IL-1R-a</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Targets&diff=4458Targets2007-11-30T21:18:53Z<p>JohnIrwin: </p>
<hr />
<div>Targets for ligand discovery can be [[enzymes]], [[receptors]], or [[protein-protein surfaces]], although these are very challenging for small molecules due to the lack of deep invaginations that are usually required for tight small molecule binding. [[Allosteric sites]] on each of the above are also possible targets, in principle.</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Enzymes&diff=1496Enzymes2007-11-30T21:18:05Z<p>JohnIrwin: </p>
<hr />
<div>Enzymes generally make excellent [[targets]] for small molecule ligand discovery because <br />
<br />
* they are pre-organized to carry out a reaction and thus have destabilizing unsatisfied residues that are available for ligand binding<br />
* there is often a chemical starting point available in the form of the endogenous ligand<br />
* there is hope that interfering with catalysis will have an effect because a bound ligand directly competes with the natrual substrate.<br />
<br />
<br />
Back to [[targets]].<br />
<br />
[[Category:Biology]]<br />
[[Category:Vocabulary]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Receptors&diff=4259Receptors2007-11-30T21:14:09Z<p>JohnIrwin: </p>
<hr />
<div>For naming of receptors, please refer to the <br />
[http://www.iuphar-db.org/index.jsp IUPHAR database ]<br />
<br />
For screening data on GPCR receptors, please see <br />
the [http://pdsp.med.unc.edu/ NIMH Psychoactive Drug Screening Program (PDSP)]<br />
<br />
<br />
Back to [[targets]].<br />
<br />
[[Category:Jargon]]<br />
[[Category:Biology]]</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Targets&diff=4457Targets2007-11-30T21:13:24Z<p>JohnIrwin: </p>
<hr />
<div>Targets for ligand discovery can be [[enzymes]], [[receptors]], or [[protein-protein surfaces]], although these are very challenging for small molecules due to the lack of deep invaginations that are usually required for tight small molecule binding.</div>JohnIrwinhttp://wiki.docking.org/index.php?title=Receptors&diff=4258Receptors2007-11-30T21:11:22Z<p>JohnIrwin: </p>
<hr />
<div>For naming of receptors, please refer to the <br />
[http://www.iuphar-db.org/index.jsp IUPHAR database ]<br />
<br />
For screening data on GPCR receptors, please see <br />
the [http://pdsp.med.unc.edu/ NIMH Psychoactive Drug Screening Program (PDSP)]</div>JohnIrwin