Friday, November 30, 2012

Atom Mappings for Reactions

Starting with Pathway Tools version 16.5, atom mapping data is available for a large number of MetaCyc reactions. Atom mapping describes for each atom of a reactant (excluding hydrogen) its corresponding atom in the product. Implicitly, atom mapping illustrates which bonds are broken and created during the reaction. The reaction page displays atom mappings by using matching colors for atoms and bonds, between reactants and products, and/or numbers labelling the atoms. If a bond is broken or made by the reaction, the bond is black.  Atom mappings are shown on the desktop as well as in Web server mode, for Firefox and Chrome browsers.  Unfortunately, the support for SVG, used for Web reaction display, is not good enough in Internet Explorer and Safari, such that those browsers do not currently show the atom mappings.

The atom mappings were computed using the technique described in Latendresse et al., "Accurate atom-mapping computation for biochemical reactions", J. Chem. Inf. Model., September 2012.  A prerequisite for computing atom mappings is canonicalizing the order of atoms in each compound structure.  This means that an invariant atom order is determined that is independent of variations of how the structure is drawn.  InChi strings are used to perform this canonicalization.  All compounds in MetaCyc were canonicalized, and an InChi executable is bundled with the 16.5 distributions, to allow automatic canonicalization when curators create new compound structures with the Marvin editor.

While the atom mappings are stored in MetaCyc, they can also be displayed in another PGDB, such as EcoCyc, for a reaction identical to one in MetaCyc.  For this to work correctly, the compound structures in the other PGDB also have to be canonicalized, or else the MetaCyc atom mappings will not match.  We have propagated the canonicalized compounds to many of the Tier2 PGDBs of our BioCyc collection.  However, most of Tier3 and PGDBs created by outside users are unlikely to have been updated yet in this regard.

Users of Pathway Tools can fix this problem in the following way for a given PGDB.  Select the menu command Tools->Propagate MetaCyc Data Updates, which will bring up a dialog panel.  This operation, discussed in the User Guide, updates compound structures and reactions with the latest data from MetaCyc.  After this, display of atom mappings should work in the updated PGDB.

Please tell us how you like the atom mappings, and any interesting insights and uses of them that you find.  We would also be interested in reports where computed atom mappings do not in fact correspond to experimentally determined mappings, such that the computational method can be further improved.