Command Line Interface (CLI) Quickstart¶

This chapter provides step-by-step introductions on how to use the SilcsBio Command Line Interface (CLI). Example commands assume a Bash shell is being used.

SILCS Simulations Using the CLI¶

Set the environment variables required to access the software:
```
export GMXDIR=<gromacs/bin>
export SILCSBIODIR=<silcsbio>
```
Set up the SILCS simulations:
```
${SILCSBIODIR}/silcs/1_setup_silcs_boxes prot=<Protein PDB>
```
To determine if the setup is complete check that the 10 PDB files required for the simulations are available using the command ls 1_setup/*_silcs.*.pdb
Submit the SILCS GCMC/MD jobs to the queue:
```
${SILCSBIODIR}/silcs/2a_run_gcmd prot=<Protein PDB>
```
This will submit 10 jobs to the queue. To check job progress, use:
```
${SILCSBIODIR}/silcs/check_progress
```
This will provide a summary list of the SILCS jobs consisting of the full job path, the job number, the task ID, the job status, and the current/total number of GCMC/MD cycles. Job status values are Q for queued, R for running, E for successfully completed, F for failed, and NA for not submitted.
Generate FragMaps:

When the GCMC/MD jobs are finished, generate FragMaps with:
```
${SILCSBIODIR}/silcs/2b_gen_maps prot=<Protein PDB>
```
This command will submit 10 jobs to the queue for calculating the occupancy maps from individual runs. Once they are done, run the following command:
```
${SILCSBIODIR}/silcs/2c_fragmap prot=<Protein PDB>
```
This will create a silcs_fragmap_<Protein PDB> folder, which contains the final FragMap files as well as scripts for visualization with external software. Please see Visualizing SILCS FragMaps for detailed instructions on visualizing your SILCS FragMaps.

For additional details, please see SILCS Simulations.

SSFEP simulations Using the CLI¶

Set the environment variables required to access the software:
```
export GMXDIR=<gromacs/bin>
export SILCSBIODIR=<silcsbio>
```
Set up the SSFEP simulations:
```
${SILCSBIODIR}/ssfep/1_setup_ssfep lig=<Ligand Mol2/SDF file> prot=<Protein PDB>
```
To determine if the setup is completed check that the PDB files required for the simulations are available using the command ls 1_setup/*/*_gmx_wat.pdb. The listing should show PDB files for the ligand alone and for the protein–ligand complex.
Submit the SSFEP MD simulation jobs to the queueing system:
```
${SILCSBIODIR}/ssfep/2_run_md_ssfep lig=<Ligand Mol2/SDF file> prot=<Protein PDB>
```
This will submit 10 jobs to the queue, 5 for the protein–ligand complex and 5 for the ligand. To check job progress, use:
```
${SILCSBIODIR}/ssfep/check_progress
```
This will provide a summary list of the SSFEP jobs consisting of the full job path, the job number, the task ID, the job status, and the current/total number of SSFEP cycles. Job status values and their meanings are listed as follows: Q (queued), R (running), E (successfully completed), F (failed), and NA (not submitted).
Calculate $\Delta \Delta G$ of ligand with selected modifications:

When the SSFEP MD simulation jobs are finished, use the ligand modification files to submit the $\Delta \Delta G$ calculations.
```
${SILCSBIODIR}/ssfep/3a_setup_modifications lig=<Ligand Mol2/SDF file> prot=<Protein PDB> mod=<modification file>
```
This command will submit 10 jobs, each of which processes one of the MD trajectories for all modifications in the modification file. Depending on the number and sizes of the modifications, this step may take minutes to several hours to complete.

Once completed, use the following command to collate the results for all of the modifications:
```
${SILCSBIODIR}/ssfep/3b_calc_ddG_ssfep mod=<modification file>
```
This command will create a lig_decor.csv file, which contains the free energy change for each modification relative to the parent ligand. SSFEP is designed to evaluate small modifications and results are best interpreted qualitatively. Therefore it is recommended that only the sign of the change, and not the magnitude, be used to inform decision making: values less than 0 indicate a modification predicted to be favorable.

For additional details, please see SSFEP: Single Step Free Energy Perturbation.