Example Commands

This section has a series of example BROOD command-line executions. Most BROOD runs are carried out using vBROOD. Each example is followed by a brief description of its behavior.

If you would like to execute the following examples as written, the appropriate paths to the executable file and the database file must be included. In addition, the query file q1.oeb will need to be in the working directory.

prompt> brood -queryMol q1.oeb -db chembl31

This command will execute BROOD with the default parameters. The file q1.oeb is opened as the query, and the database is read from the chembl31 folder. The default hitlist will be written to brood_hitlist.oeb.gz, using the default -prefix argument “brood”. Similarly, the informational output files brood_hitlist_rpt.csv, brood_log.txt and brood_parm.txt will also be written.

prompt> brood -queryMol q1.oeb -db chembl31 -prefix 4dfr

This command is the same as the previous except that the prefix to all of the output files has been changed from “brood” to “4dfr” (for example, the log file will be written to 4dfr_log.txt rather than brood_log.txt.

prompt> brood -param 4dfr_param.txt

This execution of BROOD will read all the command-line arguments from the file 4dfr_param.txt. Every time BROOD is executed, a param file is generated that can be used to exactly reproduce the run (vida infra). This option is most useful when the job is set up in vBROOD and the query and param file are written out for later execution. Using the command detailed here with a query and param file from vBROOD will give the same results as running the search from within vBROOD.

prompt> brood -param 4dfr_param.txt -ringOnly false

This example illustrates two points; that command-line arguments take precedence over arguments in the .param file, and that the -ringOnly flag is an important flag in altering BROOD results. This command line will execute BROOD with the parameters from “4dfr_param.txt”, but the -ringOnly parameter will be overridden (taking precedence) over the -ringOnly parameter that is specified in 4dfr_param.txt. A similar outcome could be achieved by editing 4drf_param.txt in a text editor, but this command-line alteration is a more direct means to the same behavior.

By default, BROOD only returns fragments that have at least two ring atoms on the shortest path between attachment points, or at least three ring atoms total if there is only one attachment point. This example shows that a user can turn off this constraint using the -ringOnly flag. If one wants to generate results that only avoid the rings as described above, one can pass -1 to the -ringOnly parameter.

prompt> brood -queryMol q1.oeb -db chembl31 -quickLook

This execution will use the query in q1.oeb to search the fragments in the database chembl31. The use of the -quickLook parameter will limit the search to approximately 2 minutes. The parameter is a great way to get a quick notion of interesting results. The databases are organized to allow rapid identification of some interesting results. The full search can take minutes to hours, and is often more appropriate when designing molecules that may take days or weeks to synthesize, nevertheless, in an iterative design session, it can be useful to quickly generate ideas using the -quickLook parameter.

prompt> brood -queryMol q1.oeb -db chembl31 -neutralpH false -tautomers false

When BROOD is building analogs by putting similar fragments into a molecular framework, sometimes the electronic environment of certain functional groups change dramatically (amines converted to amides for instance). To properly handle these cases, it is useful for BROOD to normalize the ionization and tautomer states of the new molecules before generating the final hitlist. In some cases users are better served without these normalizations. The ionization and tautomer normalizations can be turned off with the -neutralpH and -tautomer flags respectively.

prompt> brood -queryMol q1.oeb -db chembl31 -linkOnly

By default, BROOD compares the shape, chemistry, electrostatics and attachment geometry of fragments in order to suggest analog molecules. For some applications, such as joining fragments or closing rings, it is useful to build fragments into empty space. In these cases, one wants to only compare the attachment geometry of fragments, in a manner similar to the original CAVEAT searches [Lauri-1994]. The -linkOnly flag instructs BROOD to compare fragments using only their ability to form low-energy bridges between attachment points.

prompt> brood -queryMol q1.oeb -db chembl31 -property false

By default, BROOD filters the final analog hitlist with a series of property filters, each specified with a pair of range parameters. While this can be useful, on some occasions, users prefer to avoid all of the property filters. By passing false to the -property flag, all of the property filters can be turned off in one easy step.