[Dock-fans] Fixing protonation state

John J. Irwin jji at cgl.ucsf.edu
Thu Nov 1 10:50:28 PDT 2007


Hi Asdrubal

That molecule has more rotatable bonds (13 in a row, 17 total, + limited
sampling on the 2 amides) than I feel comfortable with. It also has
molecular weight > 600. These are two reason why the ZINC upload server
just won't take it. I have to draw the line somewhere, and I regret to
say you have hit it.

I would be skeptical of anyone who docks a molecule having 17 (or even
13) rotatable bonds and gets the crystallographic pose within 2A rmsd.
Actually, my skepticism starts at around 8 rotatable bonds, but I keep
it mostly to myself till we get past 12. ;-)

Almost for sure, you are trying to dock into two distinct pockets, and
the long aliphatic chain is a linker between them. My suggestion is
therefore to dock each end separately. Shoot for something with 7
rotatable bonds, even a bit less if you can. Then you can model in the
rest of the linker between them.

Good luck, and sorry to disappoint.

John


burgosgu at ualberta.ca wrote:
> Hi everybody,
>
> I need to have a compound correctly protonated to dock it. I tried to  
> use the resource of
> "upload sets" of ZINC, but it seems that it does not have the required  
> charactersitics of
> bioavailability and non-toxicity, because it gives me no output as it  
> did with other
> compounds.
>
> The smile for this compound is:
> C1=C(C=CC2=C1C(=C[N]2)CC(=O)NCCCNCCCCNCCCNC(=O)CC3=C[N]C4=C3C=C(C=C4)Br)Br
>
> Any suggestions??
>
> THANKS,
>
> Asdrubal
>
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>   


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