DOCK Blaster:Tutorial 2 - Revision history

Frodo: /* Literature Cited */

2014-03-12T03:23:17Z

Literature Cited

← Older revision		Revision as of 03:23, 12 March 2014
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	= Literature Cited =		= Literature Cited =
	We refer you to our publications pages for theory and practice of docking and virtual screening.		We refer you to our publications pages for theory and practice of docking and virtual screening.
	* [[Publications:DOCK]]
	* [[Publications:ZINC]]
	* [[Publications:DUD]]
	* [[Publications:Reviews_and_opinion]]
	* [[Publications:Targets]]

	Document status: working tutorial. Please correct any errors you may find.		Document status: working tutorial. Please correct any errors you may find.

Therese: 7 revisions

2012-10-08T20:02:12Z

7 revisions

← Older revision	Revision as of 20:02, 8 October 2012
(No difference)

JohnIrwin at 04:23, 4 December 2007

2007-12-04T04:23:52Z

← Older revision		Revision as of 04:23, 4 December 2007
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			'''DOCK Blaster Tutorial 1. Docking Methotrexate (MTX) to Dhihydrofolate Reductase (DHFR)''' A[[DOCK Blaster:Tutorials \| DOCK Blaster Tutorial]].
			{{TOCright}}
			[[Image:1dfr.jpg\|thumb\|right\|Mineralocorticoid receptor, PDB 1drf]]

			= Specific Aims =
			This tutorial will show you how to retrospectively dock a crystallographically observed ligand, aldosterone, into the human mineralocorticoid receptor, PDB code
			[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:

			* 1. Can DOCK Blaster re-dock the native ligand close to its crystallographically observed position, with a competitive score?
			* 2. Can DOCK Blaster enrich known actives from a database of property-matched decoys?
			* 3. Can DOCK Blaster suggest novel, commercially available ligands for MR?

			[[Image:Mtx.png\|thumb\|right\|Methotrexate, the crystallographically observed ligand of DHFR in 3dfr]]

			= Background and Significance =
			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.


			= Preliminary Results =
			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.

			== Protocol 1 - Prepare input files ==
			* 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]]).

			[[Image:DBtut1_1f.jpg\|thumb\|right\|Figure T1.1 - Prepare input and launch job]]

			== Protocol 2 - Submit job and review results ==
			* 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.
			** a. In the "Target" field, select the receptor, rec.pdb.
			** b. In the next field, select "Docked ligand" and select the ligand, xtal-lig.mol2.
			** c. In the "Actives" field, select the actives.smi file.
			** d. In the "Inactives" field, select the inactives.smi file.
			** e. In "Email for reports", enter your email address (optional).
			** f. In the "Aim of this experiment" field, write a short memo about what you are doing.
			** g. Check your input, and click "DOCK!" when you are ready.

			If you have followed the steps above, your screen should now look something like Figure Tut1-1 (right).
			[[Image:DBtut1_2f.jpg\|thumb\|right\|Figure T1.2 - Scrutinizer - data are uploaded, checked, and the job is started]].

			* 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.

			* 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.

			* 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.

			* 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.

			* P2.6 Review Calibration results. blah blah blah.
			[[Image:DBtut1_3f.jpg\|thumb\|right\|Figure T1.3]]




			= Proposed Research =
			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.

			== Protocol 3. Dock purchasable fragments ==

			== Protocol 4. Review and interpret docking ==

			== Protocol 5. Prioritize for testing ==

			== Protocol 6. Suggested variations ==

			== Possible problems & other approaches ==

			[[Image:DBtut1_4f.jpg\|thumb\|right\|Figure T1.4]]

			= Literature Cited =
			We refer you to our publications pages for theory and practice of docking and virtual screening.
			* [[Publications:DOCK]]
			* [[Publications:ZINC]]
			* [[Publications:DUD]]
			* [[Publications:Reviews_and_opinion]]
			* [[Publications:Targets]]

			Document status: working tutorial. Please correct any errors you may find.

			[[Category:DOCK Blaster]]
			[[Category:Tutorials]]


















	{{TOCright}}		{{TOCright}}
	'''DOCK Blaster Tutorial 1. Docking Methotrexate (MTX) to Dhihydrofolate Reductase (DHFR)'''		'''DOCK Blaster Tutorial 1. Docking Methotrexate (MTX) to Dhihydrofolate Reductase (DHFR)'''

JohnIrwin at 18:20, 21 September 2007

2007-09-21T18:20:15Z

← Older revision		Revision as of 18:20, 21 September 2007
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	== Possible problems and alternative approaches ==		== Possible problems and alternative approaches ==


			[[Category:DOCK Blaster]]
			[[Category:Tutorials]]

JohnIrwin at 22:19, 18 April 2007

2007-04-18T22:19:03Z

@@ Line 1: / Line 1: @@
 This is one of the [[DOCK Blaster:Tutorials]].
-== DOCK arylsulfonamide to carbonic anhydrase ==
+** 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.
-=== Conceptual Overview ===
+** 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
-=== Literature References ===
+** 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]]
-=== From Theory to Action ===
+** 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.
-=== Acquire Sample Data ===
+** 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.
-=== Launch Preliminary Calculation ===
+== Examining the Results ==
-=== Examining the Results ===
+== Docking a Database ==
-=== Docking a Database ===
+== Browsing and interpreting the results ==
-=== Follow up, variations ===
+== Follow up and variations ==
-=== Possible problems and alterative strategies ===
+== Possible problems and alternative approaches ==

JohnIrwin at 14:56, 21 December 2006

2006-12-21T14:56:44Z

← Older revision		Revision as of 14:56, 21 December 2006
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	This is one of the [[DOCK Blaster:Tutorials]		This is one of the [[DOCK Blaster:Tutorials]].

	== DOCK arylsulfonamide to carbonic anhydrase ==		== DOCK arylsulfonamide to carbonic anhydrase ==

JohnIrwin at 14:56, 21 December 2006

2006-12-21T14:56:33Z

← Older revision		Revision as of 14:56, 21 December 2006
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	This is one of the [[DOCK Blaster:Tutorials].		This is one of the [[DOCK Blaster:Tutorials]

	== DOCK arylsulfonamide to carbonic anhydrase ==		== DOCK arylsulfonamide to carbonic anhydrase ==

JohnIrwin at 14:56, 21 December 2006

2006-12-21T14:56:23Z

← Older revision		Revision as of 14:56, 21 December 2006
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			This is one of the [[DOCK Blaster:Tutorials].

	== DOCK arylsulfonamide to carbonic anhydrase ==		== DOCK arylsulfonamide to carbonic anhydrase ==
	This is an example of docking to Zn metalloenzymes.		This is an example of docking to Zn metalloenzymes.

JohnIrwin at 14:55, 21 December 2006

2006-12-21T14:55:56Z

New page

== DOCK arylsulfonamide to carbonic anhydrase ==
This is an example of docking to Zn metalloenzymes.

=== Conceptual Overview ===
* question 1.
* question 2.

=== Literature References ===

=== From Theory to Action ===

=== Acquire Sample Data ===

=== Launch Preliminary Calculation ===
** step 1
** step 2
** step 3
** step 4
** step 5

=== Examining the Results ===

=== Docking a Database ===

=== Follow up, variations ===

=== Possible problems and alterative strategies ===