ADL: Rigid five-member rings are driving me crazy

Ruth Huey rhuey at scripps.edu
Fri Jan 27 09:56:54 PST 2006


Oleg Stroganov wrote:

>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.
>
>  
>
Hi,
AutoDock treats each rotatable bond separately. It does not support 
cooperative changes of dihedrals.
Therefore, it is not possible to allow rotatable bonds in rings because 
there is no mechanism for keeping the ring intact.

Oleg's suggestion of constructing several pdbq-files with different 
conformations is the best solution!

         Ruth

>>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
>--------------------------------------------
>
>________________________________________________
>--- ADL: AutoDock List  --- http://www.scripps.edu/pub/olson-web/doc/autodock/ ---
>
>
>  
>



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