Introduction to AARON: Screening Ligands
The simplest and most common way to use AARON is to predict stereoselectivities for different catalysts/ligands for a given reaction.
This could be substituted analogs of a single ligand or different ligand scaffolds, or both. We'll cover each of these uses below. For each, we'll use an existing TS library (see the current structures available in the TS Library). See Building a TS Library for instructions on building your own TS library.
For all of these examples, we'll use a simplified version of an organocatalyzed allylation reaction (see REF). This is a simple reaction with a single, well-defined elementary step that is stereocontrolling. The structures in the TS library for this reaction are catalyzed by 2,2'-bipyridine-N,N'-dioxide. For this reaction, one should consider a total of 10 TS structures: 5 leading to the (R)-alcohol and 5 leading to (S), which correspond to different arrangements of the substrate and catalyst around a hexacoordinate silicon. However, for these examples we will compute only the four lowest-lying TS structures (R/ts2, S/ts1, S/ts2, and S/ts3) to speed up the examples (for real applications, it is advisable to compute all of the TS structures in the TS library!).
The lowest-lying TS structure (R/ts2) is shown below:
The other three structures in this library can be viewed here
First, let's consider the case screening different substituted versions of the ligand/catalyst found in the TS library.
We'll make predictions for two substituted bipyridine-N,N'-dioxides in which we've replaced hydrogen atoms 18 and 21 of the ligand with F).
Note: When specifying the substitution of ligand atoms, the numbers are the atom numbers for the ligand only!
reaction_type=Allylation template=NN-dioxide_example charge=1 method=b97d denfit=true basis=6-31G &Ligands Cat1: 18=F 21=F &
The reaction_type and template keywords are required, as is the 'Ligands' section. All other keywords are optional, and will default to the values found in $HOME/.aaronrc (if it exists) or $QCHASM/Aaron/.aaronrc
This input file requests that we use the TS structures from
$QCHASM/Aaron/TS_geoms/Allylation/NN-dioxide_example
The only keywords are the charge, denfit, method, and basis set. We need to specify the charge (+1), since the default charge in $QCHASM/Aaron/.aaronrc is neutral (0). The basis set is set to 6-31G to make these examples run a little more quickly. We use B97D with density fitting (denfit=true).
The input file above requests that Aaron compute all 4 TS structures found in the TS library for the catalyst Cat1 constructed by replacing atoms 18 and 21 of the ligand present in the TS library with F atoms .
Note that we can use any name we'd like to specify the ligands/catalysts (i.e. Lig19, cat19a, etc).
Save the above input file to example1.in and then run
Aaron example1.in
AARON will first make the directory Cat1 then construct a directory tree mimicking that found in the TS library for this reaction:
R/ ts2/ S/ ts1/ ts2/ ts3/AARON will then proceed through a prescribed series of 5 different steps to locate and characterize each TS structure, printing an updated status for each TS structure as it proceeds.
For instance, here is the status update after these jobs have been running for some time:
Status for all jobs...(Fri Aug 10 07:36:27 2018) -------------------------------------------------------------------------------- Status for Cat1 jobs...... Pending jobs: Cat1/R/ts2 step 1 attempt 1: No msg recorded Cat1/S/ts1 step 1 attempt 1: No msg recorded Cat1/S/ts2 step 1 attempt 1: No msg recorded Cat1/S/ts3 step 1 attempt 1: No msg recorded Aaron will check status of all jobs after 300 seconds Sleeping...
AARON lists running, pending, and finished jobs for each catalyst/ligand. Currently, all four jobs are pending for 'step 1'.
Also reported is the number of 'attempts' that have been made for the current step. Attempts refers to the number of times AARON has had to restart this particular step. For later steps, AARON will also report the number of 'cycles'. A new cycle is started any time AARON needs to return to a previous step in order to correct an erroneous geometry.
When there are running jobs, the 'Progress' section reports the Maximum Force, RMS Force, Maximum Displacement, and RMS Displacement along with whether or not these are converged for the current geometry optimization step:
Cat1/R/ts1 step 2 attempt 1 cycle 1. Progress: 0.009347/NO, 0.000378/YES, 0.037218/NO, 0.000089/YES
If you wish to examine any particular input (.com) or output (.log) file, these can be readily located within the directory structure built by AARON. These files are named according to the ligand/catalyst name, stereoisomer, TS number, and the step number.
For instance,
Cat1.R.ts1.1.com Cat1.R.ts1.1.log
are the input and output files for Step 1 (a quick semi-empirical optimization of the newly-added substituents) for TS1(R) for Cat1.
AARON will automatically check the status of all jobs every 5 minutes (by default). If a job has completed, it will automatically be advanced to the next Step. If any problems are detected with a job (an error in the output file, a structure in which connectivity has changed, etc.) AARON will attempt to fix the problem and will re-submit a new job automatically.
In this way, AARON minimizes wasted CPU time, since problems with optimizations are detected and corrected within 5 minutes.
After each 5 minute update, AARON will print relative and absolute energies, enthalpies, etc. for any completed optimizations to a '_thermo' file (e.g. example1_thermo.dat).
AARON can be killed and restarted without issue. AARON writes it's current state to a hidden file called .status after each 5 minute update. As such, it's best to kill AARON when 'sleeping' to avoid killing AARON while it is in the middle of writing this file. AARON uses .status when restarted. Because of this, if you decide to delete previous AARON files and 'start over' in a given directory, make sure you also delete .status!
AARON is designed to run continuously, so it is best to run AARON using screen or another, similar utility. See Using Screen.
Next, let's consider the case of screening different a different catalyst as well as a substituted analog of this catalyst. We will again use the organocatalyzed allylation reaction.
We'll replace the bipyridine-N,N'-dioxide found in the TS library with a biisoquinoline-N,N'-dioxide. We'll run both the unsubstituted case and that with atoms at the 3,3'-positions (atoms
reaction_type=Allylation template=NN-dioxide method=b97d basis=b97d charge=1 &Ligands Cat1: 18=F 21=F Cat2: ligand=bi-isoquinoline-NN-dioxide & &Substrates Sub1: 14=CN &
In this case, we are making predictions for two catalysts and two substrates. The first substrate is that contained in the TS library, which is run by default. AARON will also compute all TS structures for substrate 'Sub1' constructed by replacing atom 14 of the substrate with CN. Note that it will not actually start running calculations for the 'new' substrate until the structures for the original substrate have been optimized--these structures are then used as the templates for the new substrate.
The final results should be as follows: