[Dock-fans] Fixing protonation state

Francesco Pietra chiendarret at yahoo.com
Thu Nov 1 14:08:49 PDT 2007


Is your skepticism only about the precision of docking (with large, flexible
molecules) or is any evidence that also the region of receptor where docking is
found may be false? E.g. helix S5 instead of S6 in a pore?
Thanks
francesco pietra

--- "John J. Irwin" <jji at cgl.ucsf.edu> wrote:

> 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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> > http://blur.compbio.ucsf.edu/mailman/listinfo/dock-fans
> >   
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