MUG '04 -- 24 - 27 Feb, 2004

Magnet: from Prototype to Product

Hanneke Jansen
Chiron, Inc.


The Magnet prototype was previously described at MUG01. This toolkit was developed to analyze docking output with respect to characteristics used when eyeballing docking results: hydrogen bonds to the active site, occupancy of specific pockets in the binding site, and % of the ligand surface area buried by docking. Magnet generates descriptors for each docking, which can be used to sort and select the more interesting docking results. An iterative process of defining important features, sorting the output, and reviewing the results, gradually pulls the most attractive dockings to the top of the list. Using the insights gained with respect to the binding site and the different binding modes that are observed, the Magnet columns can be used to derive a new, quantitative scoring function which is tailor-made with respect to the specific binding site and set of compounds under investigation.

The Magnet prototype was developed in SPL and showed great promise, leading to a Chiron-Metaphorics collaboration. In this collaboration, Metaphorics developed a new version of Magnet. This version is a complete re-implementation of the method and uses Metaphorics and Daylight toolkits to provide structure handling and rule matching. A new language named SEA was developed and is used for the description of intermolecular interactions. The new Magnet version is much faster and more flexible than the prototype. Some examples include the ability to deal with shallow binding sites by calculating accessible surface area only for atoms that are not in VDW-contact with the protein, and various ways of defining pocket occupancy.

Presentation slides:

Daylight Chemical Information Systems, Inc.