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DOCK Blaster Tutorials
== Introduction to Tutorials ==
DOCK Blaster tutorials are designed to illustrate the use of DOCK Blaster using real-world examples, with data drawn from and referenced to the literature. They are written in a way that we imagine you might actually use DOCK Blaster in a real project. We also offer [[DOCK Blaster:Protocols | protocols]], which are designed to illustrate in cookbook form many more of the tasks that may be carried out with [[DOCK Blaster]].


== 1. DOCK MTX to DHFR (example of cofactor) ==
Each tutorial is self-contained:
** 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. [[Image:Tut1-1.jpg|thumb|right|Figure Tut1-1]]
* contains pointers to available data to use
* points to relevant literature
* has a conceptual summary of the scientific question
* includes detailed step-by-step instructions, including pictures
* describes variations, possible problems, and suggestions for additional steps you may like to try
 
== 1. DOCK MTX to DHFR ==
=== Conceptual Overview ===
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.
* Question 1. Is DOCK Blaster able to suggest other compounds from a commercially available library that might be active against dihydrofolate reductase?
** Sub-question 1.1. Is DOCK Blaster able to re-dock MTX close to its crystallographically observed position, with a competitive score?
** 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?
** Sub-question 1.3. Is DOCK Blaster able to enrich known actives, and de-enrich known inactives, against DHFR?
 
=== From Theory to Action ===
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.
 
=== Launch Preliminary Calculation ===
** 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.  
** 2. Click on "Start docking!" to go to the input preparation page.
** 2. Click on "Start docking!" to go to the input preparation page.
** 3. Click on "HELP" to open up the documentation for input preparation in a separate window.  
** 3. Click on "HELP" to open up the documentation for input preparation in a separate window.  
Line 13: Line 32:
** 4. Click on the first "Browse" button (to the right of Target) and select the rec.pdb file you just downloaded.  
** 4. Click on the first "Browse" button (to the right of Target) and select the rec.pdb file you just downloaded.  
** 5. In the next field "docked ligand" select the xtal-lig.mol2 file.
** 5. In the next field "docked ligand" select the xtal-lig.mol2 file.
** 6. Optionally, you may select the actives.smi and inactives.smi from the next two lines. [[Image:Tut1-2.jpg|thumb|right|Figure Tut1-2]]
** 6. Optionally, you may select the actives.smi and inactives.smi from the next two lines.  
** 7. Enter your email address if you wish to receive progress reports by email.
** 7. Enter your email address if you wish to receive progress reports by email.
** 8. Enter a brief comment about the calculation.  
** 8. Enter a brief comment about the calculation.  
Line 19: Line 38:


If you have followed the steps above, your screen should now look something like Figure Tut1-1 (right).
If you have followed the steps above, your screen should now look something like Figure Tut1-1 (right).
[[Image:Tut1-1.jpg|thumb|center|Figure Tut1-1]]


** 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.  
** 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.  
[[Image:Tut1-2.jpg|thumb|center|Figure Tut1-2]]


** 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.
** 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.
Line 26: Line 47:
** 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=
** 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=


** 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]]
** 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]]


** 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.  
** 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.  


** 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.
** 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.
=== Examining the Results ===
=== Docking a Database ===




== 2. DOCK X to carbonic anhydrase (example of metalloenzyme) ==
=== 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 ===




== 2. DOCK X to carbonic anhydrase (example of metalloenzyme) ==




== 3. DOCK to target X, but no ligand available ==
== 3. DOCK to target X, but no ligand available ==
=== Conceptual Overview ===
* question 1.
* question 2.
=== From Theory to Action ===
=== Acquire Sample Data ===
=== Launch Preliminary Calculation ===
=== Examining the Results ===
=== Docking a Database ===


== 4. DOCK to Y, many controls available ==  
== 4. DOCK to Y, many controls available ==  
=== 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 ===
== 5. No title yet ==
=== Conceptual Overview ===
* question 1.
* question 2.
=== Literature References ===
=== From Theory to Action ===
=== Launch Preliminary Calculation ===
** step 1
** step 2
** step 3
** step 4
** step 5
=== Examining the Results ===


== 5. ==
=== Docking a Database ===

Revision as of 01:13, 21 December 2006

Introduction to Tutorials

DOCK Blaster tutorials are designed to illustrate the use of DOCK Blaster using real-world examples, with data drawn from and referenced to the literature. They are written in a way that we imagine you might actually use DOCK Blaster in a real project. We also offer protocols, which are designed to illustrate in cookbook form many more of the tasks that may be carried out with DOCK Blaster.

Each tutorial is self-contained:

  • contains pointers to available data to use
  • points to relevant literature
  • has a conceptual summary of the scientific question
  • includes detailed step-by-step instructions, including pictures
  • describes variations, possible problems, and suggestions for additional steps you may like to try

1. DOCK MTX to DHFR

Conceptual Overview

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.

  • Question 1. Is DOCK Blaster able to suggest other compounds from a commercially available library that might be active against dihydrofolate reductase?
    • Sub-question 1.1. Is DOCK Blaster able to re-dock MTX close to its crystallographically observed position, with a competitive score?
    • 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?
    • Sub-question 1.3. Is DOCK Blaster able to enrich known actives, and de-enrich known inactives, against DHFR?

From Theory to Action

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'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.

Launch Preliminary Calculation

    • 1. Go to DOCK Blaster web page blaster.docking.org. Please note that during pre-alpha testing this page is different. Contact John Irwin for details.
    • 2. Click on "Start docking!" to go to the input preparation page.
    • 3. Click on "HELP" to open up the documentation for input preparation in a separate window.
      • 3.1. In the documentation window, click on "Sample Data" at the end of the first paragraph.
      • 3.2 In the sample data window, click on the link to data.docking.org
      • 3.3. Click on DUD40.
      • 3.4. Click on CDK2.
      • 3.5. Right mouse to save all five files in this directory on your disk.
      • 3.6. Close the documentation window, returning to the DOCK Blaster input form.
    • 4. Click on the first "Browse" button (to the right of Target) and select the rec.pdb file you just downloaded.
    • 5. In the next field "docked ligand" select the xtal-lig.mol2 file.
    • 6. Optionally, you may select the actives.smi and inactives.smi from the next two lines.
    • 7. Enter your email address if you wish to receive progress reports by email.
    • 8. Enter a brief comment about the calculation.
    • 9. (optional: enter cofactor.par below)

If you have followed the steps above, your screen should now look something like Figure Tut1-1 (right).

Figure Tut1-1
    • 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.
Figure Tut1-2
    • 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.
    • 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.
      Figure Tut1-3
    • 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.
    • 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.

Examining the Results

Docking a Database

2. DOCK X to carbonic anhydrase (example of metalloenzyme)

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

3. DOCK to target X, but no ligand available

Conceptual Overview

  • question 1.
  • question 2.

From Theory to Action

Acquire Sample Data

Launch Preliminary Calculation

Examining the Results

Docking a Database

4. DOCK to Y, many controls available

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

5. No title yet

Conceptual Overview

  • question 1.
  • question 2.

Literature References

From Theory to Action

Launch Preliminary Calculation

    • step 1
    • step 2
    • step 3
    • step 4
    • step 5

Examining the Results

Docking a Database