Subject: ligand binding

From: Christian Pilger <[email-masked]>
Date: Thu, 19 Oct 2000 15:01:38 +0200

Dear CCl'ers,

I am performing docking studies employing AUTODOCK 3. Due to its size
and conformational flexibility, I ususally get more then one suggestion
for meaningful orientation/conformation within the proposed binding site
of the enzyme for a given inhibior structure. These are subsequentely 
ranked by AUTODOCK's implemented empirical free energy function. However
when using a different empirical scoring scheme (e.g. SCORE by Wang et 
al.) on the suggested inhibitor/enzyme complexes, frequently the order
is altered, leading to a different hypothesis for the active conformation
of the considered inhibitor.

In order to make the "correct" selection (the Xray structure of the
complex of the lead compound/enzyme is known) out of the proposed binding
modes for a single inhibitor, I would like to employ other methods for
ranking these. I'm aware of such methods like FEP, but I don't have much
experience in running molecular dynamics calculations.

I would like to extend the results obtained for the lead compound to a
dataset of structurally related compounds to get an hypothesis for the
active conformation for each. Finally, I'd like to compare the binding
affinities among the candidates of my dataset.

My request to the members of this list:

Can somebody provied me with useful hints, webpages, books, howto's, or
other references to methods suitable for the relative ranking of proposed
binding modes of a single inhibitor ? Would it be possible to extend this
somehow to the dataset (about 20 compounds) ?

I have access to AMBER 6.

Regards,

Christian

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 Christian Pilger                      Uni-GH Paderborn
                                       FB 13 - Organische Chemie
                                       Warburger Str. 100
                                 
                                       D-33098 Paderborn/Germany
 Tel.: 05251-60279/-602183         
 Fax : 05251-603245         email: [email-masked]

 Word Wide Web: 	   http://oc30.uni-paderborn.de/~cpilger
 
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