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| == DOCK methotrexate to Dihydrofolate reductase ==
| | '''DOCK Blaster Tutorial 1. Dock to Human Thyroid Hormone Receptor Beta-1 (TR beta)''' |
| This is one of the [[DOCK Blaster:Tutorials]].
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| === Conceptual Overview ===
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| 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.
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| * Question 1. Is DOCK Blaster able to suggest other compounds from a commercially available library that might be active against dihydrofolate reductase?
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| ** Sub-question 1.1. Is DOCK Blaster able to re-dock MTX close to its crystallographically observed position, with a competitive score?
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| ** 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?
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| ** Sub-question 1.3. Is DOCK Blaster able to enrich known actives, and de-enrich known inactives, against DHFR?
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| picture of MTX
| | A[[DOCK Blaster:Tutorials | DOCK Blaster Tutorial]]. |
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| picture of 3dfr
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| picture of MTX bound to 3dfr | | ==Step 1== |
| | a. Browse to the DOCK Blaster main page: |
| | http://blaster.docking.org/ |
| | and select '''Start with a PDB code''' from the '''DOCK''' pull down menu: |
| | http://blaster.docking.org/parser.shtml |
| | b. In the PDB code field, enter 1N46, the PDB code for TR beta. |
| | http://www.ebi.ac.uk/msd-srv/oca/oca-bin/ocashort?id=1N46 |
| | Click on '''DOCK''' to start. |
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| picture of other DHFR ligands
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| === From Theory to Action ===
| | If you are really impatient you can do all of the above |
| 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.
| | by simply clicking here: |
| | http://blaster.docking.org/cgi-bin/parser.pl?code=1N46 |
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| === Launch Preliminary Calculation === | | ==Step 2== |
| ** 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.
| | You will get a confirmation page showing that the target has been looked up correctly at the PDB. To proceed, click on "DOCK". Write down the DOCK Blaster Job ID number. You will need it. The docking process is now queued, and may have started if the system is not overloaded. |
| ** 2. Click on "Start docking!" to go to the input preparation page.
| | [[File:DOCK_Blaster_step1a.png|300px|center]] |
| ** 3. Click on "HELP" to open up the documentation for input preparation in a separate window.
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| *** 3.1. In the documentation window, click on "Sample Data" at the end of the first paragraph.
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| *** 3.2 In the sample data window, click on the link to data.docking.org
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| *** 3.3. Click on DUD40.
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| *** 3.4. Click on CDK2.
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| *** 3.5. Right mouse to save all five files in this directory on your disk.
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| *** 3.6. Close the documentation window, returning to the DOCK Blaster input form.
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| ** 4. Click on the first "Browse" button (to the right of Target) and select the rec.pdb file you just downloaded.
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| ** 5. In the next field "docked ligand" select the xtal-lig.mol2 file.
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| ** 6. Optionally, you may select the actives.smi and inactives.smi from the next two lines.
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| ** 7. Enter your email address if you wish to receive progress reports by email.
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| ** 8. Enter a brief comment about the calculation.
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| ** 9. (optional: enter cofactor.par below)
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| If you have followed the steps above, your screen should now look something like Figure Tut1-1 (right).
| | ==Step 3== |
| [[Image:Tut1-1.jpg|thumb|center|Figure Tut1-1]]
| | Click on the link to browse progress at the bottom of the page |
| | http://blaster.docking.org/cgi-bin/jobwatch.pl?job_id=35605&pin= |
| | (replace the job number with your actual job number. This one will not work) |
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| ** 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.
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| [[Image:Tut1-2.jpg|thumb|center|Figure Tut1-2]]
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| ** 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.
| | Step 4. When the job has finished, you will be in the "Calibration Done" state as shown in the progress bar with the yellow paint near the top of the page. You will see a report that reports how well docking worked. |
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| ** 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/jobwatch.pl?job_id=32&pin=
| | Step 5. Interpreting the calibration summary table |
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| ** 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|center|Figure Tut1-3]]
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| ** 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.
| | Step 6. Inspecting further details and poses of the ligand and decoys. |
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| ** 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.
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| === Examining the Results ===
| | Step 7. Launching a docking job |
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| === Docking a Database ===
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| === Follow up, variations ===
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| === Possible problems and alterative strategies === | | |
| | = Literature Cited = |
| | We refer you to our publications pages for theory and practice of docking and virtual screening. |
| | Document status: working tutorial. Please correct any errors you may find. |
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| | [[Category:DOCK Blaster]] |
| | [[Category:Tutorials]] |
DOCK Blaster Tutorial 1. Dock to Human Thyroid Hormone Receptor Beta-1 (TR beta)
A DOCK Blaster Tutorial.
Step 1
a. Browse to the DOCK Blaster main page:
http://blaster.docking.org/
and select Start with a PDB code from the DOCK pull down menu:
http://blaster.docking.org/parser.shtml
b. In the PDB code field, enter 1N46, the PDB code for TR beta.
http://www.ebi.ac.uk/msd-srv/oca/oca-bin/ocashort?id=1N46
Click on DOCK to start.
If you are really impatient you can do all of the above
by simply clicking here:
http://blaster.docking.org/cgi-bin/parser.pl?code=1N46
Step 2
You will get a confirmation page showing that the target has been looked up correctly at the PDB. To proceed, click on "DOCK". Write down the DOCK Blaster Job ID number. You will need it. The docking process is now queued, and may have started if the system is not overloaded.
Step 3
Click on the link to browse progress at the bottom of the page
http://blaster.docking.org/cgi-bin/jobwatch.pl?job_id=35605&pin=
(replace the job number with your actual job number. This one will not work)
Step 4. When the job has finished, you will be in the "Calibration Done" state as shown in the progress bar with the yellow paint near the top of the page. You will see a report that reports how well docking worked.
Step 5. Interpreting the calibration summary table
Step 6. Inspecting further details and poses of the ligand and decoys.
Step 7. Launching a docking job
Literature Cited
We refer you to our publications pages for theory and practice of docking and virtual screening.
Document status: working tutorial. Please correct any errors you may find.
