Coupled optimization in protein docking

Here, we introduce a new approach to macromolecular docking which combines the continuous global optimization algorithm CGU with the grid-based conformational search engine DOT. We also detail the use of this method to dock acetylcholine into the fasciculin-acetylcholinesterase complex. Fasciculin blocks access to the long, narrow pathway leading to the active site, which is located in the interior of the acetylcholinesterase. For this reason, finding the location computationally is rather non-trivial. We not only successfully identified the optimal docking configuration, but were able to do so in a matter of hours.