DOCK Blaster:Tutorials: Difference between revisions

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== Introduction to Tutorials ==
'''Introduction'''
DOCK Blaster 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. They are scripted in a way that we imagine you might actually use DOCK Blaster for research. We also offer [[DOCK Blaster:Protocols | protocols]], which are designed to illustrate in a more abstract form many more of the tasks that can be performed using [[DOCK Blaster]].


Each tutorial contains:
*NOTE: these tutorials did not get finished before the paper appeared in J Med Chem. Please manage as best you can until we write them properly*
* has a conceptual summary of the scientific questions being investigated
* pointers to relevant literature
* a consideration of the practical details in adapting theory to calculation
* pointers to available data to use
* step by step instructions, with screenshots, describing how to proceed
* a guide to how to evaluate and use the results
* suggestions of follow up experiments, variations
* a consideration of problems that may occur and what to do about them


== DOCK MTX to DHFR ==
We have tried to identify projects that are *representative* of common projects, *illustrative* of the features and weaknesses of [[DOCK Blaster]] as it currently stands, and *didactic*, in as much as they illustrate how we imagine this service should be used.
=== 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?


picture of MTX
{{TOCright}}


  picture of 3dfr
You do not need to run a tutorial before you use DOCK Blaster, but we recommend it and it will not take long. Scan the list and try to pick an example that resembles your current project, in terms of available information and perhaps target class, ligand chemistry, or binding site situation.  Please see also the [[DOCK Blaster:Preliminaries | preliminary considerations]] article for the "big picture". The categories of targets we will consider are:  nuclear receptor, enzyme, metallo-enzyme, kinase, GPCR.  The types of problems we consider are : good information, minimal information, insufficient information, and excessive information.  The level of effort for the tutorial is either  easy, moderate, or hard.


picture of MTX bound to 3dfr
= [[DOCK Blaster:Tutorial 1 | Dock to human thyroid hormone beta-1]] =
* Target category: Nuclear receptor
* Effort: Easy
* Problem type: Minimal information
* PDB code: 1N46


picture of other DHFR ligands
= [[DOCK Blaster:Tutorial 2 | Dock to minearalocorticoid receptor (MR)]] =
* Target category: Nuclear receptor
* Effort: Medium
* Problem type: Minimal information
* PDB code: XXXX


=== From Theory to Action ===
A [[nuclear hormone receptor]], drawn from [[DUD]], that illustrates the use of DOCK Blaster when both actives and inactive controls are available.
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 ===
= [[DOCK Blaster:Tutorial 3 | Dock methotrexate (MTX) to dihydrofolate reductase (DHFR)]] =
** 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.
** 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).
* Target category: Nuclear receptor
[[Image:Tut1-1.jpg|thumb|center|Figure Tut1-1]]
* Effort: Medium
* Problem type: Minimal information
* PDB code: XXXX


** 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.
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.
[[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.


** 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=
= [[DOCK Blaster:Tutorial 4 | Dock to angiotensin II converting enzyme (ACE)]] =


** 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]]
* Target category: Nuclear receptor
* Effort: Medium
* Problem type: Minimal information
* PDB code: XXXX


** 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.  
This case, also from [[DUD]], illustrates the use of DOCK Blaster on zinc metalloenzymes.


** 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.
= [[DOCK Blaster:Tutorial 5 | Only apo structure available]] =


=== Examining the Results ===
* Target category: Nuclear receptor
* Effort: Medium
* Problem type: Minimal information
* PDB code: XXXX


=== Docking a Database ===
DOCK to cruzain, a cystein protease target for Chagas' Disease, for which only an apo structure is available.
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.


=== Follow up, variations ===
= [[DOCK Blaster:Tutorial 6 | No crystal structure available]] =


=== Possible problems and alterative strategies ===
* Target category: Nuclear receptor
* Effort: Medium
* Problem type: Minimal information
* PDB code: XXXX




== DOCK X to carbonic anhydrase (example of metalloenzyme) ==
DOCK to a target for which no crystal structure is available.
=== Conceptual Overview ===
Describes the use of Blast/Modbase to obtain and evaluate a structure.
* question 1.
Describes checking the model of the target for suitability for docking.
* question 2.
=== Literature References ===


=== From Theory to Action ===
= [[DOCK Blaster:Tutorial 7 | Multiple crystal structures available]] =


=== Acquire Sample Data ===
* Target category: Nuclear receptor
* Effort: Medium
* Problem type: Minimal information
* PDB code: XXXX


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


=== Examining the Results ===
Multiple crystal structures available.
Multiple actives and inactives available.
How to optimise the use of DOCK Blaster for this case.


=== Docking a Database ===
You are welcome to write new tutorials - this IS a wiki! You are also welcome to suggest new tutorials, to support at docking.org.


=== Follow up, variations ===
[[Category:DOCK Blaster]]
 
[[Category:Tutorials]]
=== Possible problems and alterative strategies ===
 
 
 
 
== 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 ===
 
=== Follow up, variations ===
 
=== Possible problems and alterative strategies ===
 
 
 
 
== 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 ===
 
=== Follow up, variations ===
 
=== Possible problems and alterative strategies ===
 
 
 
 
 
== 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 ===
 
=== Follow up, variations ===
 
=== Possible problems and alterative strategies ===

Latest revision as of 20:02, 8 October 2012

Introduction

  • NOTE: these tutorials did not get finished before the paper appeared in J Med Chem. Please manage as best you can until we write them properly*

We have tried to identify projects that are *representative* of common projects, *illustrative* of the features and weaknesses of DOCK Blaster as it currently stands, and *didactic*, in as much as they illustrate how we imagine this service should be used.

You do not need to run a tutorial before you use DOCK Blaster, but we recommend it and it will not take long. Scan the list and try to pick an example that resembles your current project, in terms of available information and perhaps target class, ligand chemistry, or binding site situation. Please see also the preliminary considerations article for the "big picture". The categories of targets we will consider are: nuclear receptor, enzyme, metallo-enzyme, kinase, GPCR. The types of problems we consider are : good information, minimal information, insufficient information, and excessive information. The level of effort for the tutorial is either easy, moderate, or hard.

Dock to human thyroid hormone beta-1

  • Target category: Nuclear receptor
  • Effort: Easy
  • Problem type: Minimal information
  • PDB code: 1N46

Dock to minearalocorticoid receptor (MR)

  • Target category: Nuclear receptor
  • Effort: Medium
  • Problem type: Minimal information
  • PDB code: XXXX

A nuclear hormone receptor, drawn from DUD, that illustrates the use of DOCK Blaster when both actives and inactive controls are available.

Dock methotrexate (MTX) to dihydrofolate reductase (DHFR)

  • Target category: Nuclear receptor
  • Effort: Medium
  • Problem type: Minimal information
  • PDB code: XXXX

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.


Dock to angiotensin II converting enzyme (ACE)

  • Target category: Nuclear receptor
  • Effort: Medium
  • Problem type: Minimal information
  • PDB code: XXXX

This case, also from DUD, illustrates the use of DOCK Blaster on zinc metalloenzymes.

Only apo structure available

  • Target category: Nuclear receptor
  • Effort: Medium
  • Problem type: Minimal information
  • PDB code: XXXX

DOCK to cruzain, a cystein protease target for Chagas' Disease, for which only an apo structure is available. 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.

No crystal structure available

  • Target category: Nuclear receptor
  • Effort: Medium
  • Problem type: Minimal information
  • PDB code: XXXX


DOCK to a target for which no crystal structure is available. Describes the use of Blast/Modbase to obtain and evaluate a structure. Describes checking the model of the target for suitability for docking.

Multiple crystal structures available

  • Target category: Nuclear receptor
  • Effort: Medium
  • Problem type: Minimal information
  • PDB code: XXXX


Multiple crystal structures available. Multiple actives and inactives available. How to optimise the use of DOCK Blaster for this case.

You are welcome to write new tutorials - this IS a wiki! You are also welcome to suggest new tutorials, to support at docking.org.

Retrieved from "http://wiki.docking.org/index.php?title=DOCK_Blaster:Tutorials&oldid=1098"