Enumerating Reactants and Products

A typical use case for AutoTS is to compute the barrier of a reaction as a function of some chemical modification of one or more reactants. To do this you must enumerate the chemical modifications of interest on at least one reactant and one product, pair these structures, and run AutoTS jobs on each pairing. An easier way to achieve this enumeration would be to enumerate the chemical modifications on the reactants only and perform a specified transformation to generate products. The utility AutoTSReaction performs this task for a small number of predefined transformations, including some multi-step ones. In the case of a multi-step reaction a reactant and product pair is written for each step so that an AutoTS job can be run for any reaction step. For a description of the syntax and options for this utility, see AutoTSReaction Command Help.

Reactions can have multiple steps, and each step is defined by a reaction SMARTS. Additionally, default reactants are defined by SMILES strings. In any multi-step reaction, at least one of the products in step i must map to a reactant at step i+1. Reactions must be selected, by name, through the command line argument -reaction_type. You can define custom reaction types by creating a custom Json reaction file (though it is best to request a new reaction type from the AutoTS development team).

Once a reaction is selected you should provide reactant molecules in Maestro files with the argument -reactant_file. If no reactant molecules are given, default reactants are used. Any given reactants must be superstructures of the SMARTS strings in the defining reaction SMARTS. All chemical modifications of a distinct reactant species must be in the same reactant file and each distinct reactant is required to be in a different file. As a concrete example consider the predefined reaction type “Michael-Addition-Thiolate”, which is the transformation shown below.

All chemical modifications of the first reactant should contain a thiolate group and should be placed in a single file (e.g. r1.mae). All chemical modifications of the second reactant should contain an enone and should be placed in a second file (e.g. r2.mae). You can then transform the two reactants into a single product using the following command.

$SCHRODINGER/utilities/AutoTSReaction -reaction_type Michael-Addition-Thiolate \
    -reactant_file r1.mae r2.mae -file_mode PRODUCTS -jobname michael_addition

The argument -file_mode determines how the reactants in the files are combined. The value PRODUCTS specifies that the reactants should be combined in all ways (a pairwise loop for two reactants). For each pair of reactants a set of files will be written for reactants and products. Optionally, you can specify a template AutoTS input file in order to write an AutoTS input file for each set of reactants and products. See AutoTSReaction Command Help for more details.