Rapid Mapping of All Atoms in Biochemical Reactions

The Science

In the design and bioengineering of metabolic pathways for clean bioenergy and other applications, it is important to understand and eventually manipulate the movement of atoms in these biochemical reactions. For example, assessing how a reactant compound is transformed into a targeted product allows researchers to optimize for efficiency in the pathways. A new computational system (Minimum Weighted Edit-Distance or MWED) allows mapping of all the non-hydrogen atoms in biochemical reactions from the initial reactants to the final products. MWED relies on predicting the propensity of forming or breaking chemical bonds during a biochemical reaction. It then calculates and optimizes all possible solutions to the reaction of interest. Because it also uses a mixed-integer linear programming technique, it is three-fold faster than other, similar techniques. The MWED all atom pathway mapping was benchmarked on 2,446 manually curated biochemical reactions from the KEGG database. The researchers found that only 22 MWED-predicted reactions were in error (error rate of 0.9%) due mainly to difficulties in representing stereochemistry in the reactions. MWED offers research scientists an extremely fast and highly accurate method to model all atoms in biochemical reactions, both for novel bioengineering as well as for tracking isotopically labeled atoms in metabolic experiments.

The Impact

In systems biology, the accurate atom mapping of biochemical reactions is fundamental for many applications. For example, atom mappings can be used to compute the number of carbon atoms conserved when a source compound is transformed to a target compound in an engineered metabolic pathway to determine the efficiency of the pathway. Atom mappings can also be used to track atoms in the isotope labeling experiments that have been commonly used to elucidate metabolic pathways for decades. Atom mappings can also be used to visually color corresponding atoms in reaction diagrams to make reaction mechanisms more visually apparent.


The complete atom mapping of a chemical reaction is a bijection of the reactant atoms to the product atoms that specifies the terminus of each reactant atom. Atom mapping of biochemical reactions is useful for many applications of systems biology, in particular for metabolic engineering where synthesizing new biochemical pathways has to take into account for the number of carbon atoms from a source compound that are conserved in the synthesis of a target compound. Rapid, accurate computation of the atom mapping(s) of a biochemical reaction remains elusive despite significant work on this topic. In particular, past researchers did not validate the accuracy of mapping algorithms. Researchers introduce a new method for computing atom mappings called the minimum weighted edit-distance (MWED) metric. The metric is based on bond propensity to react and computes biochemically valid atom mappings for a large percentage of biochemical reactions.


Latendresse, M., J. P. Malerich, M. Travers, and P. D. Karp. 2012. “Accurate Atom-Mapping Computation for Biochemical Reactions,” Journal of Chemical Information and Modeling, DOI: 10.1021/ci3002217.