ADL: Rigid five-member rings are driving me crazy

Oleg Stroganov stroganov at belozersky.msu.ru
Fri Jan 27 09:46:16 PST 2006


Hello, Trevor

I suggest that the only way to handle partial flexibility of
5-membered rings in autodock is to construct several pdbq-files
with different conformations of rings and feed each conformer to
separate docking procedure. Making ring-bonds rotable is
problematic because a) usually in conformation transitions participate
more than 1 rotable bond, so you have to account cooperative changes of
dihedrals, and not every random structure generated by autodock be reasonable;
and b) you have to set tight limits for values of dihedrals of
ring-bonds because you cannot rotate them from -180 to 180
degrees - it will explode your ligand.

> Can somebody please point me to, for example, a document, which would help
> me figure out how to make a 5 member ring act as the (partly) flexible
> entity it is, rather than staying flat, or a boat, or a chair. For example
> one would like to allow (partial) boat-to-chair conversion, as in
> cyclohexane, if the surrounding forces supported such a structure.

> I have taken a close look at the  .out.pdbq  ligand files, and it seems it
> wouldn't be too hard to sit down and manually map out a ligand file making
> the ring-bonds rotatable, but what would be the effect on Autodock? Would
> it still produce reliable docks?

> Additionally, is there some elegant way to handle isomers? It is getting a
> pain to produce up to 16 ligand files for each of the ligand structures I
> am studying, one for each combination of isomeric bond possibilities (since
> I am studying in-vivo structures I need to consider all isomers - the
> Thalidomide disaster instructs us in what happens when you forget the isomers)

I'd recommend you to use some free chemical drawing software, which
allows to save molecules to .mol-files - at least, drawing 16 isomers will be
less tiresome. Then pull these mol-files through PRODRG and you'll get
pdbqs for each isomer of your molecule.


> Sincerely
> Trevor

> ------------------------------------
> Trevor G Marshall, PhD
> Autoimmunity Research Foundation
> +1-(805)492-3693
> -----------------------------------
> ________________________________________________
> --- ADL: AutoDock List  ---
> http://www.scripps.edu/pub/olson-web/doc/autodock/ ---


Sincerely,
Oleg V. Stroganov,

--------------------------------------------
Oleg V. Stroganov
PhD stud., Moscow State University,
fac. of Bioengineering and Bioinformatics
--------------------------------------------



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