:: _cmdline:

cosolvkit command line interface

The CosolvKit command line interface is the easiest method to create and simulate a cosolvent system. If this is your first time learning about CosolvKit, take a look at the page Get started.

CosolvKit inputs

The script create_cosolvent_system.py provide all the necessary tools to build a cosolvent system and optionally run an MD simulation with standard setup. The main entry point of the script is the file config.json where all the necessary flags and command line options are specified. A template for the config.json can be found in cosolvkit/data/config.json. Cosolvents and forcefields templates can be found in the folder cosolvkit/data/ as well.

CosolvKit config.json structure

Argument	Type	Description	Default value	OPENMM	AMBER	GROMACS	CHARMM
cosolvents	string	Path to the json file containing the cosolvents to add to the system.	no default
forcefields	string	Path to the json file containing the forcefields to use.	no default
md_format	string	Format to use for the MD simulations and topology files. Supported formats: [OPENMM, AMBER, GROMACS, CHARMM]	no default
receptor	boolean	Boolean describing if the receptor is present or not.	no default
protein_path	string	If receptor is true this should be the path to the protein structure.	no default
clean_protein	boolean	Flag indicating if cleaning the protein with PDBFixer	TRUE
keep_heterogens	boolean	Flag indicating if keeping the heterogen atoms while cleaning the protein. Waters will be always kept.	FALSE
variants	dictionary	Dictionary of residues for which a variant is requested (different protonation state) in the form {“chain_id:res_id”:”protonation_state”}, None for the rest of the residues.	empty dictionary
add_repulsive	boolean	Flag indicating if adding repulsive forces between certain residues or not.	FALSE	✔️	✖️	✖️	✖️
repulsive_resiudes	list	List of residues for which applying the repulsive forces.	empty list	✔️	✖️	✖️	✖️
epsilon	float	Depth of the potential well in kcal/mol	0.01 kcal/mol	✔️	✖️	✖️	✖️
sigma	float	inter-particle distance in Angstrom	10.0 Angstrom	✔️	✖️	✖️	✖️
solvent_smiles	string	Smiles string of the solvent to use.	H2O
solvent_copies	integer	If specified, the box won’t be filled up with solvent, but will have the exact number of solvent molecules specified.	no default
membrane	boolean	Flag indicating if the system has membranes or not.	FALSE
lipid_type	string	If membrane is TRUE specify the lipid to use. Supported lipids: [“POPC”, “POPE”, “DLPC”, “DLPE”, “DMPC”, “DOPC”, “DPPC”]	“POPC”
lipid_patch_path	string	If the lipid required is not in the available, it is possible to pass a pre-equilibrated patch of the lipid of interest.	no default
cosolvent_placement	integer	Integer deciding on which side of the membrane to place the cosolvents. Available options: [0 -> no preference, 1 -> outside, -1 -> inside]	0
waters_to_keep	list	List of indices of waters of interest in a membrane system.	no default
radius	float	If no receptor, the radius is necessary to set the size of the simulation box.	no default
output	string	Path to where save the results.	no default
run_cosolvent_system	boolean	Flag indicating if running creating the system or not.	TRUE
run_md	boolean	Flag indicating if running the md simulation after creating the system or not.	FALSE	✔️	✖️	✖️	✖️

CosolvKit can be run with and without protein (receptor), variants for the protonation states can be specified in the form of a python dictionary and custom repulsive forces can be specified between specific molecules in the system. The flag run_cosolvent_system decides if a new cosolvent system will be created, while the run_md flag takes care of running the MD simulation using the standard protocol provided by CosolvKit and generate trajectories (please note that this task is resources and time intensive depending on the hardware).

Post-processing pipeline

The script post_simulaiton_processing.py takes care of analysing the MD simulation trajectories and produces RDF plots as well as densities analysis as PyMol sessions. To access help message type:

$ post_simulation_processing.py --help

The script is based on the Report class and the following functions:

• log_file: is the statistics.csv or whatever log_file produced during the simulation. At least Volume, Temperature and Pot_e should be reported on this log file.

• traj_file: trajectory file

• top_file: topology file

• cosolvents_file: json file describing the cosolvents

generate_report():

• out_path: where to save the results. 3 folders will be created:

  • report

    • autocorrelation

    • rdf

generate_density_maps():

• out_path: where to save the results.

• analysis_selection_string: selection string of cosolvents you want to analyse. This follows MDAnalysis selection strings style. If no selection string, one density file for each cosolvent will be created.

generate_pymol_report()

• selection_string: important residues to select and show in the PyMol session.

Example of an RDF plot generated with the post-processing pipeline.

Example of a statistics plot generated with the post-processing pipeline.

Outputs

CosolvKit generates topology and positions files that will be used to run the MD simulation, the output format is decided by the field md_format in the config file.

Access help message

$ create_cosolvent_system.py --help