Absolute Binding Free Energy Calculations

Here, we’ll run a quick absolute binding free energy calculation for benzene bound to T4 Lysozyme. For this, we’ll use the bss_abfe_multi_isomer workflow through its CLI, which requires only an SDF file containing all required ligands, and the pdb of the protein. Check the options with

bss_abfe_multi_isomer -h

Copy over the required input:

mkdir bss_abfe_example
cd bss_abfe_example
cp ../tests/data/benzene.sdf .
cp ../tests/data/t4l.pdb .

Now, let’s run a relatively very short (but still fairly expensive) ABFE calculation with 0.01 ns of sampling per production window. Note that you currently need to provide the absolute path to your inputs:

bss_abfe_multi_isomer --lig_sdfs_file <INSERT ABSOLUTE PATH TO benzene.sdf> \
                      --protein_pdb_path <INSERT ABSOLUTE PATH to t4l.pdb> \
                      --run_time_abfe 0.01 \
                      --dump_to . \

The results (see the log or results.json in the dump directory) should show a binding free energy of around -5 kcal/mol.

Running through the command line with this many arguments is unweildy, and some options aren’t available through the CLI (for example, the lambda spacing). It’s likely a better option to write a quick script - using the pre-made workflow directly in python - simply import the workflow factory , customise the options, and run (all in a python script):

from maize.graphs.exs.biosimspace.abfe_single_node import get_abfe_multi_isomer_workflow
workflow = getabfe_multi_isomer_workflow()

# Set workflow options...

# Run
workflow.execute()