  Motivation: The design of enzymes is as challenging as it is consequential
for making chemical synthesis in medical and industrial applications more
efficient, cost-effective and environmentally friendly. While several aspects
of this complex problem are computationally assisted, the drafting of catalytic
mechanisms, i.e. the specification of the chemical steps-and hence intermediate
states-that the enzyme is meant to implement, is largely left to human
expertise. The ability to capture specific chemistries of multi-step catalysis
in a fashion that enables its computational construction and design is
therefore highly desirable and would equally impact the elucidation of existing
enzymatic reactions whose mechanisms are unknown. Results: We use the
mathematical framework of graph transformation to express the distinction
between rules and reactions in chemistry. We derive about 1000 rules for amino
acid side chain chemistry from the M-CSA database, a curated repository of
enzymatic mechanisms. Using graph transformation we are able to propose
hundreds of hypothetical catalytic mechanisms for a large number of unrelated
reactions in the Rhea database. We analyze these mechanisms to find that they
combine in chemically sound fashion individual steps from a variety of known
multi-step mechanisms, showing that plausible novel mechanisms for catalysis
can be constructed computationally.
