My research is the virtual screening of some ligands as a new inhibitor of β-secretase (BACE1) so, I should to compare the best docking result with native crystal structure , We have two forms of BACE1, close conformation of the flap region and open conformation of the flap region.
When I got to review the structures of BACE1 in protein database bank, I found these results. All structures of the BACE1-bound Pseudopeptide inhibitors are close conformation of the flap region and structures of the BACE1-bound non-peptidomimetic inhibitors are open conformation of the flap region.
The problem is that the my ligands binds to the close conformation of the flap region so I don't have any non-peptidomimetic inhibitors crystallographic structure to compare with my ligands.
What should I do?
Maybe you could find some valuable information in:
http://www.bch.msu.edu/~kuhn/publication_papers/pdf/Zavodszky_Kuhn_Proteins06.pdf
As per your explanation it is hard to conclude that what exactly you are asking. Can you be more precise so that i may suggest a possible work flow.
My ligand is a coumarin and I should to compare my docking result with crystalographic structure of close conformation of BACE1+inhibitor
Inhibitor should have a structure similar to coumarin but I can not find a structure similar to coumarin in protein data bank Because all inhibitors are pseudopeptide structure.
I apologize for my bad English.
Please correct me if I misunderstood your problem. It sounds like you have a compound that you tested with unknown binding to your protein of interest. As a result, you do not have a crystal structure with a similar ligand bound that you can compare to determine if your docking was successful. If this is your problem, you have to consider expected interactions when assessing the success of your docking. It sounds as though crystal structures are available with other ligands. If you catalog that information, determine similarities and differences between known binders (things that bind experimentally to your protein), and look for similarities in protein-ligand interactions, you should be able to build a check list of interactions that must be present for the compound to be a binder. You can then do distance measurements between the heavy atoms of your compounds and the selected residues in order to determine binding.
I hope this addresses your question and helps in some way.
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