DOCK Blaster:Preliminaries: Difference between revisions

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Docking requires three things: a target, a database, and a docking program.  [[DOCK Blaster]] uses [[DOCK 3.5.54]] as the docking program and [[ZINC]] as the database. You must choose the target.
To use [[DOCK Blaster]] you must choose a target structure for docking. You will also need to have some idea of the binding site you wish to target, as proteins often contain more than one eligible site. You may also have additional information such as actives and inactives, which can be useful for assessing docking performance.
To use [[DOCK Blaster]] you must choose a target structure for docking. You will also need to have some idea of the binding site you wish to target, as proteins often contain more than one eligible site. You may also have additional information such as actives and inactives, which can be useful for assessing docking performance.



Revision as of 02:16, 12 February 2009

Docking requires three things: a target, a database, and a docking program. DOCK Blaster uses DOCK 3.5.54 as the docking program and ZINC as the database. You must choose the target.

To use DOCK Blaster you must choose a target structure for docking. You will also need to have some idea of the binding site you wish to target, as proteins often contain more than one eligible site. You may also have additional information such as actives and inactives, which can be useful for assessing docking performance.

Here we consider the most common scenarios for a docking project, and attempt to point out what you should keep in mind before you start docking. Remember, this is research! So be sure to do controls if you can, and be skeptical!

We hope this page will give you some useful guidance on how to get started, but remember it is only a guide! Once you have considered the relevant scenarios on this page, and you have files for the receptor and a binding site specification on hand, then you should proceed to DOCK_Blaster:Prepare_Input.

Crystal structure, ligand bound

This is a nice situation to be in. Your target is in a ligand bound conformation, and your ligand is a valuable control with which to assess performance. Although there are many reasons why docking may still be problematic, you at least have a good chance of being able to evaluate how well the docking program performs, and whether it can be expected to predictive.

Crystal structure, apo

This is often a close runner up to having a ligand bound crystal structure, as in many cases there is not a lot of induced fit. It may be worth looking for crystal structures of highly similar targets, in case one has a ligand bound. That might give an indication of the amount of induced fit in the target that might be expected on ligand binding. A drawback to this scenario is the lack of a crystallographic control. It may be worthwhile trying to model in a ligand, if you know one.

No crystal structure, but a homology model

Homology models vary widely in their usefullness for docking. This is a topic of considerable current interest. Generally, the higher the identity of the target to the scaffold the more reliable the model will be. Pay attention to amino acid substitutions in the binding site. Also, if several scaffolds are available, consider the sequence identity in the binding site as well as the overall sequence identity as a figure of merit for selecting the best model for docking.

No crystal structure, but an NMR structure

NMR structures can also be useful for docking, particularly if the binding site is fairly rigid. Ligand controls can be helpful for assessing the performance of the docking.

No crystal structure, and the homology model is of fair or unknown quality

We do not like to discourage you from docking, but it is only fair to warn you that the odds are against you in this scenario.

I don't have a target structure and do not know how to proceeed

You cannot start docking without a 3D atomic model of your target. Ask colleages for advice. Search the PDB or use ModBase.

Muliple crystal structures - which one?

You are both lucky and cursed, because you have the embarassment of riches, and yet it may be unclear which model to choose. We can make several suggestions:

  • Consider superimposing the structures to look for variability in the binding site.
  • Consider both the overall resolution and the B factors of atoms in the binding site when considering which model is best.
  • You may be able to use atoms from multiple bound ligands for the "hot spots".

I have experimental information about actives and inactives

Several sources of information:

  • positive controls (actives)
  • negative controls (inactives)

I have additional knowledge of my target not obvious from its structure

Special sources of information:

  • pH at which the structure was solved / is biologically relevant