selecting potential binding cavities with MD

From: Thomas Evangelidis (tevang3_at_gmail.com)
Date: Fri Apr 09 2010 - 14:11:21 CDT

Dear NAMD users,

This is not a technical question:

 I want to design an inhibitor to target a Nucleotide Binding Domain of a
transporter. The most obvious potential target cavity is the ATP binding
pocket which is very similar to respective pockets in other proteins and
consequently inhibition of that site in vivo will lead to a wide-spread
off-target effect. Moreover binding site prediction tools like Q-Site Finder
rank the ATP binding pocket 4th (namely there are other bigger cavities in
the protein domain), whereas SiteHound not even in the top 10.

My question is can I predict via MD if by targeting a neighboring cavity I
could block ATP binding (essentially by looking at the conformation change
in the ATP binding pocket)? And most importantly can I select the optimum
binding cavity in the same manner? For this purpose I will need to create a
dummy ligand somehow to fill the selected cavity.

I would greatly appreciate any advice!

Thomas

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