Question: Structure Based Drug Designing When Active Site Is Known But No Known Inhibitors Available Present ?
gravatar for Zak
9.0 years ago by
Zak110 wrote:

I am doing a project on structure based drug designing , and i have a protein-protein interaction site for which no known inhibitors are known and there are no related proteins with inhibitors. What should i do ?? can i use random drug like molecules from zinc database??

I would also like to know about any academic free software's for QSAR.

Thanks in advance

ppi drug docking • 3.3k views
ADD COMMENTlink modified 3.0 years ago by Biostar ♦♦ 20 • written 9.0 years ago by Zak110

so, is it a PPI surface or an active site? ..not entirely sure from title+text

ADD REPLYlink written 9.0 years ago by Michael Schubert7.0k
gravatar for Michael Schubert
9.0 years ago by
Cambridge, UK
Michael Schubert7.0k wrote:

You have got 2 choices here:

  • select a large dataset from a database of small molecules, e.g. ZINC, as you suggested
  • try to design a molecule to fit your binding pocket

To find suitable potential inhibitors, you can make use of the fact that an inhibitor is in most cases structurally related to the substrate. E.g., you could enter the substrate in ZINC and search for structures of 80% similarity as a basis of your virtual screening experiment.

For academically licensed docking tools, you can have a look at AutoDock or UCSF Dock.

edit: I missed the PPI here. The workflow is generally the same, but you of course don't have a substrate to start your search with. You could look for compounds structurally similar to a part of the interfacing area or do a random set of small molecules (which may not work too well).

ADD COMMENTlink written 9.0 years ago by Michael Schubert7.0k
gravatar for Egon Willighagen
9.0 years ago by
Egon Willighagen5.3k wrote:

For free QSAR software there are a couple of options. Part of that, is the calculation of descriptors for which you can use the Chemistry Development Kit. Bioclipse provides a graphics user interface for this (and for the JOELib and OpenTox descriptors too):

alt text

See this paper. The Bioclipse authors are working on integrating R so that you can also make regression models inside Bioclipse too.

ADD COMMENTlink written 9.0 years ago by Egon Willighagen5.3k
gravatar for Vladimir Chupakhin
9.0 years ago by
Toledo, Spain
Vladimir Chupakhin520 wrote:
  1. Define the binding site - small, big, flexible, some sites can be druggable, some not.
  2. Search similar binding site in databases with site comparison software
  3. Generate the pharmacophore for protein-protein itneraction - search with pharmacophore
  4. etc
ADD COMMENTlink written 9.0 years ago by Vladimir Chupakhin520
gravatar for Keith Callenberg
9.0 years ago by
Pittsburgh, PA
Keith Callenberg910 wrote:

There is a nice list of QSAR software, some free for academics, here:

ADD COMMENTlink modified 13 months ago by RamRS30k • written 9.0 years ago by Keith Callenberg910
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