Difference between revisions of "DOCK Blaster:FAQ"

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[[DOCK Blaster]] is a free virtual screening service. These are the frequently asked questions. Questions that take more than a few lines deserve their own wiki article.
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[[DOCK Blaster]] is a free virtual screening service. These are the frequently asked questions. Questions that take more than a few lines deserve their own wiki article.  Other FAQs are available at this site as follows:
 +
* [[ZINC:FAQ]]
 +
* [[DUD:FAQ]]
 +
* [[DOCK:FAQ]]
 +
* [[THC:FAQ]]
 +
* [[FAQ]] for everything not covered by one of those products.
  
 
= General =  
 
= General =  
  
 
== What is DOCK Blaster? ==  
 
== What is DOCK Blaster? ==  
DOCK Blaster is a free web-based service for molecular docking and virtual screening. It uses [[UCSF]] [[DOCK 3.5.54]] as a [[docking engine]], and [[ZINC]] as a [[dockable database]]. It runs entirely on the [[Cluster Information | computer cluster]] in the [[Shoichet Lab]] at [[Mission Bay]] in San Francisco. The graphical user interface comprises an expert system that is designed to help guide both novices and experts to useful results.
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DOCK Blaster is a free web-based service for molecular docking and virtual screening. It uses [[UCSF]] [[DOCK 3]] as a [[docking engine]], and [[ZINC]] as a [[dockable database]]. It runs entirely on the [[About our cluster | computer cluster ]] in the [[Shoichet Lab]] at [[Mission Bay]] in San Francisco. The graphical user interface comprises an expert system that is designed to help guide both novices and experts to useful results.
 
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{{TOCright}}
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== Is DOCK Blaster formally described in a paper? How to cite? ==
 
== Is DOCK Blaster formally described in a paper? How to cite? ==
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== Why DOCK Blaster? Docking programs have been around for ages. What's new? ==
 
== Why DOCK Blaster? Docking programs have been around for ages. What's new? ==
We are attempting to serve a constituency of investigators who would like to use docking for their projects but find the barriers to setting up their own computational lab prevent them from doing so. Experts are still welcome to use DOCK Blaster, of course. But we are really aiming to serve a broad community of biologists who seek new chemistry for their biological targets.
+
We aim to serve a constituency of investigators who would like to use docking to discover new ligands for their targets, but find the barriers to setting up their own computational lab prevent them from doing so. Experts are still welcome to use DOCK Blaster, of course. But we are really aiming to serve biologists who seek new chemistry for their biological targets.
  
 
== How do I use DOCK Blaster? ==
 
== How do I use DOCK Blaster? ==
If you have a target for which you seek ligands to test, you need a structure of your target, and an indication of the binding site for which you want to find a small molecule ligand.  It is incredibly helpful if you have either a single known ligand modeled into the binding site, or know ligands that bind. The target should be in PDB format, and must conform to certain rules (see [[Preparing Input]]. The indicatation of the binding site is ideally a docked ligand in mol2 format, but could also be residues surrounding the binding site in PDB format. Point your browser to [http://blaster.docking.org/] to get started.
 
  
If you know the PDB code of the target you wish to dock, you can simply enter it in the [[DOCK Blaster]] interface. Note: this approach currently can only work if their is an identifiable ligand in the binding site. If not, see the method above.
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Please see [[DOCK Blaster | What you need to start]].
 
+
If you would like to see DOCK Blaster work, but you don't care which target, try the "I'm feeling lucky" option.
+
  
 
== How much does DOCK Blaster cost to use? ==
 
== How much does DOCK Blaster cost to use? ==
DOCK Blaster is free for everyone. It is supported by NIH grant GM71896 (to BKS and JJI). We reserve the right to limit usage, particularly by intensive users.
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DOCK Blaster is free. It is supported by the US National Institutes of Health via grant GM71896 (to JJI and BKS). We reserve the right to limit usage by intensive users.
  
== I'm having trouble using DOCK Blaster ==
+
== What do I do if I am having trouble using DOCK Blaster? ==
Please see the [[Problems]] page for a general overview of all problems.
+
  
Please see the [[Bugs]] page for information about bugs. Please report bugs to support at docking.org.  
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If you began by uploaded a receptor file, aka "Start with a structure", by far the most common problem is with the formatting of the files.  We recommend reading [[DOCK_Blaster:Prepare_Input | this]] and also looking at some [[DOCK_Blaster:Tutorials | examples]] and also [http://data.docking.org sample data].
  
Please see the [[DOCK Blaster:Problems]] page for DOCK Blaster specific problems.
+
If you began with a PDB code, aka "Start with a PDB Code", by far the most common problem is that there is no single identifiable ligand in the fileIf this is the case, you need to download the PDB file yourself, and, specifying the binding site, use the "Start with a structure" starting point.  
   
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== Can I trust DOCK Blaster? ==
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This question warrants its own article. [[DOCK Blaster:Reliability]]
+
  
== I think DOCK Blaster has crashed ==
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If you used "I'm feeling lucky", and you are having problems, we regret that you were not more lucky.  We suggest trying "I'm feeling lucky" a couple of more times, and perhaps your luck will change.  
Please see [[DOCK Blaster:Crash]].
+
  
== I have privacy concerns about my data ==
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More detailed information about problems may be found here:
 +
 
 +
 
 +
* [[Problems]] page for a general overview of all problems.
 +
 
 +
* [[Bugs]] page for information about bugs. Please report bugs to support at docking.org.
 +
 
 +
* [[DOCK Blaster:Problems]] page for DOCK Blaster specific problems.
 +
 
 +
== Can DOCK Blaster be trusted? ==
 +
Please see [[DOCK Blaster:Reliability | this]].
 +
 
 +
== Has DOCK Blaster crashed? ==
 +
Please read [[DOCK Blaster:Crash  | this]].
 +
 
 +
== Are my data private? ==
 
Please see our [[Privacy Policy]]
 
Please see our [[Privacy Policy]]
  
== DOCK Blaster is reporting a problem that I don't think is real/legitimate ==
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== What should I do if I disagree with a decision DOCK Blaster has apparently made? ==
 +
Please write to support at docking.org explaining the problem.
  
== DOCK Blaster made completely wrong suggestions for my target ==
+
== What should I do if DOCK Blaster has made completely wrong suggestions for my target? ==
DOCK Blaster is a research tool aimed at helping people discover new ligands.
+
DOCK Blaster is a research tool that aims to help people discover new ligands.  Unfortunately, docking can fail for many reasons, as documented by an extensive literature. Our benchmarking studies (Irwin et al, J Med Chem, 2009) suggest that black box docking works on perhaps 18% of eligible targets.  Thus there is a rather high probability that your target is not among the successful ones.  Finally, it is important to remain skeptical of any docking results, whether they are produced by an expert or a machine like DOCK Blaster.
  
 
== Is there any evidence that DOCK Blaster works? ==
 
== Is there any evidence that DOCK Blaster works? ==
DOCK Blaster uses the same docking technology (DOCK 3.5.54) and database technology (ZINC) as is used in the Shoichet Lab for all their publications. Furthermore, the DUD paper (JMC 2006). Furthermore, the DOCK Blaster paper (to appear).
+
DOCK Blaster uses the same docking technology (DOCK 3) and database technology (ZINC) as is used in the Shoichet Lab for all their ([http://shoichetlab.compbio.ucsf.edu/publications.php publications]). The DUD Paper (Huang, Shoichet Irwin, J Med Chem, 2006) assessed the performance of docking, some of it fully automated. Recently, the DOCK Blaster paper (Irwin et al, J Med Chem 2009, in press) assessed fully automated docking against over 7000 targets drawn from the PDB.  The results indicate that automated docking screens produce viable-looking results perhaps 18% of the time.  Importantly, the automatic self-assessment feature of DOCK Blaster allows you to tell when this is true.
  
 
== What is your motivation to create and support DOCK Blaster? ==
 
== What is your motivation to create and support DOCK Blaster? ==
Line 53: Line 64:
  
 
== Can I get my own private copy of DOCK Blaster? ==
 
== Can I get my own private copy of DOCK Blaster? ==
If we get enough interest, we may be able to license DOCK Blaster technology. Please contact us to express your interest.
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You may request a copy of DOCK Blaster by writing to John Irwin at jji at cgl dot ucsf dot edu. We will be making the scripts available, but it will take us some time following publication (Sept 2009) to get them into a state we can release.
  
 
== Does DOCK Blaster work better on some targets than on others? ==
 
== Does DOCK Blaster work better on some targets than on others? ==
Yes. Now, which ones? The DOCK Blaster paper will explain this for 100 test systems.
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Yes. Now, which ones? The paper (Irwin et al, J Med Chem, 2009, in press) documents 1,298 targets for which DOCK Blaster produces viable-looking results. You can find these on our [http://data.docking.org website].  [http://data.docking.org/2009/TableS12.xls TableS12.xls]
  
 
== How long does DOCK Blaster take? ==
 
== How long does DOCK Blaster take? ==
Overall, we aim to get you preliminary results in an hour or. Big database docking typically takes a day or so, depending on many factors. Throughput depends on the load on our servers. Thank you for your patience!
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Submitted to an unloaded cluster, preliminary docking usually runs in 30-60 minutes. A full database screen, which may or may not be warranted by the preliminary docking, can take hours to days, depending on the binding site and the database docked. If the cluster is loaded it will obviously take longer to deliver results.  We aim to provide informative messages to manage your expectations. Thank you for your patience! More information here: [[DOCK Blaster:Timings]]
 
+
More information here: [[DOCK Blaster:Timings]]
+
  
 
== What do DOCK Blaster results mean? ==
 
== What do DOCK Blaster results mean? ==
Top scoring hits are computer generate predictions of small molecules that might bind to your protein. Our success rate against actual drug targets is on the order of 5% or less, typically. Sometimes it is zero percent! Typically, we purchase 50 compounds that we like from the top 500 for experimental testing, and typically, we find a few that bind in the micromolar range.
+
Top scoring hits from a docking screen are computer-generated predictions of small molecules that may bind to your protein. Surveying the literature, typical prediction rates from docking screens vary wildly, but are often of a rate of only a few percent, although there are famous exceptions (Doman 2002). In a typical screen, purchasing 50 compounds selected from among the top 500, we would consider ourselves fortunate if 3 compounds showed micromolar affinity.  What this means in practice is that docking hit lists should not be simply purchased willy-nilly.  We recommend holding a [[hit picking party]] to select compounds for purchase and test based on a range of opinions.  We would be astonished to see a confirmed hit rate over 10%, meaning that we expect at least 9/10 top scoring docking compounds WILL NOT BIND.  Caveat emptor.
  
 
== Can I used DOCK Blaster with a different docking program? ==
 
== Can I used DOCK Blaster with a different docking program? ==
Currently, DOCK Blaster only supports DOCK 3.5.54. It has not escaped our notice that the overall system may be appropriate for other docking engines. If this option interests you, please write us, making the case for a particular docking program.
+
Currently, DOCK Blaster only supports DOCK 3. It has not escaped our notice that the overall system may be appropriate for other docking engines. If this option interests you, please write us, making the case for a particular docking program.
 +
 
 +
== Can I used DOCK Blaster with my own database of small molecules? ==
 +
Yes, to some extent.  You can upload ligands to ZINC to create an user uploaded subset, 1000 molecules at a time.  These subsets may be docked using DOCK Blaster.  
  
== Can I used DOCK Blaster with a different database of small molecules? ==
+
A number of subsets of ZINC are available for docking.  We may be able to create large custom subsets to suit your purposes.  If you do not see what you need in the "by subset" page of ZINC, please write us at support at docking.org to discuss.
Yes, there are four ways to pick database subsets to dock.  
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* our preferred subsets
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* annotated subsets
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* uploaded subsets
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* user-created subsets
+
  
We recommend the use of the "fragment-like" and "mini-lead-like" subsets of ZINC.
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For most purposes, we recommend the use of the "fragment-like" or "lead-like" subsets of ZINC.
  
 
== Why is it called "DOCK Blaster"? ==
 
== Why is it called "DOCK Blaster"? ==
Line 82: Line 89:
  
 
== What is the history of DOCK Blaster? ==
 
== What is the history of DOCK Blaster? ==
* DOCK Blaster originates in the docking protocol used in Tack (I.D.) Kuntz's lab 1982-1993
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Please see [[DOCK Blaster:History]].
* Brian K. Shoichet modified the protocol (and DOCK!) 1989-2000
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* David M. Lorber wrote the first MakeDOCK script in 2000.
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* Binqing Wei made contributions and refinements in 2001
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* Austin N. Kirschner wrote several scripts in 2002.
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* Niu Huang did DUD (2004-2006), and made improvements
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* Preliminary work on DOCK Blaster began in 2000 by John Irwin
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* The lab has been using DOCK Blaster tools, including the GUI, since summer 2003.
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* Full alpha testing (20+ users, 4 continents) in March 2007.
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* Able to "do DUD" in September 2007.
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* Beta release in October 2007 (20-100 users).
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* The first full release (and thus the start of version 2) may be in Jan 08.
+
  
 
= Preparer / Scrutinizer Questions =  
 
= Preparer / Scrutinizer Questions =  
Line 108: Line 104:
  
  
= I have a question that is not listed here... =
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= What do I do if my question is not listed here? =
 
Please use 'search' to check the documentation, use google, or try to ask our panel of experts in the blaster-fans@docking.org mailing list. If you still can't get an answer, please write support at docking.org.
 
Please use 'search' to check the documentation, use google, or try to ask our panel of experts in the blaster-fans@docking.org mailing list. If you still can't get an answer, please write support at docking.org.
  

Latest revision as of 14:06, 5 April 2013

DOCK Blaster is a free virtual screening service. These are the frequently asked questions. Questions that take more than a few lines deserve their own wiki article. Other FAQs are available at this site as follows:

General

What is DOCK Blaster?

DOCK Blaster is a free web-based service for molecular docking and virtual screening. It uses UCSF DOCK 3 as a docking engine, and ZINC as a dockable database. It runs entirely on the computer cluster in the Shoichet Lab at Mission Bay in San Francisco. The graphical user interface comprises an expert system that is designed to help guide both novices and experts to useful results.

Is DOCK Blaster formally described in a paper? How to cite?

The performance of DOCK Blaster against benchmarking data is described in Irwin, Shoichet, Mysinger et al., "Automated docking screens: a feasibility study", J. Med. Chem (2009), in press. The documentation of the interface and the software that runs it is documented on this wiki.

Why DOCK Blaster? Docking programs have been around for ages. What's new?

We aim to serve a constituency of investigators who would like to use docking to discover new ligands for their targets, but find the barriers to setting up their own computational lab prevent them from doing so. Experts are still welcome to use DOCK Blaster, of course. But we are really aiming to serve biologists who seek new chemistry for their biological targets.

How do I use DOCK Blaster?

Please see What you need to start.

How much does DOCK Blaster cost to use?

DOCK Blaster is free. It is supported by the US National Institutes of Health via grant GM71896 (to JJI and BKS). We reserve the right to limit usage by intensive users.

What do I do if I am having trouble using DOCK Blaster?

If you began by uploaded a receptor file, aka "Start with a structure", by far the most common problem is with the formatting of the files. We recommend reading this and also looking at some examples and also sample data.

If you began with a PDB code, aka "Start with a PDB Code", by far the most common problem is that there is no single identifiable ligand in the file. If this is the case, you need to download the PDB file yourself, and, specifying the binding site, use the "Start with a structure" starting point.

If you used "I'm feeling lucky", and you are having problems, we regret that you were not more lucky. We suggest trying "I'm feeling lucky" a couple of more times, and perhaps your luck will change.

More detailed information about problems may be found here:


  • Problems page for a general overview of all problems.
  • Bugs page for information about bugs. Please report bugs to support at docking.org.

Can DOCK Blaster be trusted?

Please see this.

Has DOCK Blaster crashed?

Please read this.

Are my data private?

Please see our Privacy Policy

What should I do if I disagree with a decision DOCK Blaster has apparently made?

Please write to support at docking.org explaining the problem.

What should I do if DOCK Blaster has made completely wrong suggestions for my target?

DOCK Blaster is a research tool that aims to help people discover new ligands. Unfortunately, docking can fail for many reasons, as documented by an extensive literature. Our benchmarking studies (Irwin et al, J Med Chem, 2009) suggest that black box docking works on perhaps 18% of eligible targets. Thus there is a rather high probability that your target is not among the successful ones. Finally, it is important to remain skeptical of any docking results, whether they are produced by an expert or a machine like DOCK Blaster.

Is there any evidence that DOCK Blaster works?

DOCK Blaster uses the same docking technology (DOCK 3) and database technology (ZINC) as is used in the Shoichet Lab for all their (publications). The DUD Paper (Huang, Shoichet Irwin, J Med Chem, 2006) assessed the performance of docking, some of it fully automated. Recently, the DOCK Blaster paper (Irwin et al, J Med Chem 2009, in press) assessed fully automated docking against over 7000 targets drawn from the PDB. The results indicate that automated docking screens produce viable-looking results perhaps 18% of the time. Importantly, the automatic self-assessment feature of DOCK Blaster allows you to tell when this is true.

What is your motivation to create and support DOCK Blaster?

We felt that many investigators who would like to use virtual screening were not using it because of several barriers to entry. We hope that DOCK Blaster will fill an niche and give access to this technology to investigators who previously were put off by the requirements to set up a docking laboratory.

Can I get my own private copy of DOCK Blaster?

You may request a copy of DOCK Blaster by writing to John Irwin at jji at cgl dot ucsf dot edu. We will be making the scripts available, but it will take us some time following publication (Sept 2009) to get them into a state we can release.

Does DOCK Blaster work better on some targets than on others?

Yes. Now, which ones? The paper (Irwin et al, J Med Chem, 2009, in press) documents 1,298 targets for which DOCK Blaster produces viable-looking results. You can find these on our website. TableS12.xls

How long does DOCK Blaster take?

Submitted to an unloaded cluster, preliminary docking usually runs in 30-60 minutes. A full database screen, which may or may not be warranted by the preliminary docking, can take hours to days, depending on the binding site and the database docked. If the cluster is loaded it will obviously take longer to deliver results. We aim to provide informative messages to manage your expectations. Thank you for your patience! More information here: DOCK Blaster:Timings

What do DOCK Blaster results mean?

Top scoring hits from a docking screen are computer-generated predictions of small molecules that may bind to your protein. Surveying the literature, typical prediction rates from docking screens vary wildly, but are often of a rate of only a few percent, although there are famous exceptions (Doman 2002). In a typical screen, purchasing 50 compounds selected from among the top 500, we would consider ourselves fortunate if 3 compounds showed micromolar affinity. What this means in practice is that docking hit lists should not be simply purchased willy-nilly. We recommend holding a hit picking party to select compounds for purchase and test based on a range of opinions. We would be astonished to see a confirmed hit rate over 10%, meaning that we expect at least 9/10 top scoring docking compounds WILL NOT BIND. Caveat emptor.

Can I used DOCK Blaster with a different docking program?

Currently, DOCK Blaster only supports DOCK 3. It has not escaped our notice that the overall system may be appropriate for other docking engines. If this option interests you, please write us, making the case for a particular docking program.

Can I used DOCK Blaster with my own database of small molecules?

Yes, to some extent. You can upload ligands to ZINC to create an user uploaded subset, 1000 molecules at a time. These subsets may be docked using DOCK Blaster.

A number of subsets of ZINC are available for docking. We may be able to create large custom subsets to suit your purposes. If you do not see what you need in the "by subset" page of ZINC, please write us at support at docking.org to discuss.

For most purposes, we recommend the use of the "fragment-like" or "lead-like" subsets of ZINC.

Why is it called "DOCK Blaster"?

The name is a tribute to BLAST, the famous sequence alignment and searching tool of NCBI. And of course DOCK. If you have a better name, let us know, there is a prize. ;-)

What is the history of DOCK Blaster?

Please see DOCK Blaster:History.

Preparer / Scrutinizer Questions

Calibration Questions

Docking Questions

Results Browser and Interpretation Questions

What do I do if my question is not listed here?

Please use 'search' to check the documentation, use google, or try to ask our panel of experts in the blaster-fans@docking.org mailing list. If you still can't get an answer, please write support at docking.org.