[Chimera-users] COX inhibitor demo discrepancy

[Elaine Meng]

HI Simon,
We’re glad Chimera has been helpful in your studies!

The COX inhibitors demo (under Tools… Demos in the menu) just uses some structures from RCSB PDB that already have the small molecules in the correct locations relative to the protein structures.  It’s not really a tutorial (it doesn’t tell you how to do anything) but a series of actions in Chimera that show you parts of these existing structures.  The Credits panel of that demo says which PDB entries were used:  1cqe (COX-1 with flurbiprofen) and 6cox (COX-2 with SC-558).  So if you just start Chimera and use command “open 1cqe” for example, it will show the COX-1 complex structure.  1cqe and 6cox each contain a homodimer (two copies of the protein+ligand), but for simplicity in the demos, only monomers were shown.

I don’t know where you got the structures you opened, so the coordinates might be completely different.  I.e., maybe what you see is where DSV put the small molecules.  Also ViewDock will only display energies if what you read in to ViewDock is (1) a format that VIewDock knows, and (2) actually includes those energies.  Chimera doesn’t calculate them for you.  I have no idea what you opened in ViewDock.  Its manual page lists the types of docking outputs that it knows how to read, like from the programs DOCK, Glide, AutoDock, GOLD, etc.
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/viewdock/framevd.html>

There is a ViewDock tutorial that includes sample input from DOCK:
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/tutorials/vdtut.html>

If you meant you tried the Autodock Vina interface in Chimera and it didn’t put the small molecules in the right place, that is the way of docking calculations. There are a lot of docking parameters and setup options and sometimes adjusting those will get the right answer, or simply sampling more orientations.  Unfortunately the interface in Chimera uses a web service that doesn’t allow very much sampling.  To do a thorough docking study, you might have to obtain a docking program and run it separately from Chimera.  

However, no need to do docking for these particular molecules because the structures of the complexes are already known and publicly available from the PDB!

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                       
UCSF Chimera(X) team
Department of Pharmaceutical Chemistry
University of California, San Francisco


> On Sep 6, 2017, at 4:17 AM, simon chapman <rowanlodge19 at gmail.com> wrote:
> 
> Hi, I'm very impressed with Chimera as  a user of only 3 weeks so far
> 
> Trying out the various facilities has been a very useful exercise for completing my Masters in MedChem.
> 
> However, when I emulated  the tutorial covering COX 1 and 2 inhibition, inputting the molecules fluribrofen and SC558 I generated via DS Visualiser bind at the outside edge of  the enzymes. Not centrally as displayed in the video.
> 
> I also noted the molecular data in  ViewDock, ie: energies etc, is missing. The table is blank other than the molecule number. Selecting 'Column' etc has no effect. The 'H-bonds' option does display however.
> 
> I've probably done something  wrong, hey ho...but can you enlighten me?
> 
> Best wishes   Simon