fragPELE parameters

These are parameters to set up a fragPELE simulation.

List of fragPELE parameters:

List of examples:

frag_core

  • Description: Defines the path to PDB file containing the protein and docked scaffold.

  • Type: String

  • Default: None

Note

It is a mandatory parameter for fragPELE.

Note

The scaffold or core is the molecule on which the fragments will be inserted.

See also

Example 1, Example 4

chain_core

  • Description: Sets the unique chain id of the scaffold supplied in the frag_core structure.

  • Type: Character

  • Default: None

Note

It is a mandatory parameter for fragPELE.

Note

The scaffold, also referred to as core, is the molecule on which the fragments will be inserted.

See also

frag_core, Example 1, Example 4

frag_ligands

  • Description: Defines the path to the SDF containing fully grown ligands. Fully grown means that each ligand must contain both scaffold and fragment already attached.

  • Type: String

  • Default: None

Warning

Each ligand present in the SDF must contain the scaffold defined in the frag_core and one fragment. If the substructure searcher is not able to find the scaffold in any of the fragments, the simulation will fail.

Note

There is an alternative method to run fragPELE. Instead of supplying an SDF containing fully grown ligands, we can supply a library of fragments with a parameter called frag_library.

Note

Note that frag_ligands and frag_library parameters cannot be defined simultaneously.

See also

frag_core, chain_core, frag_library, Example 1, Example 4

frag_library

  • Description: Defines the path to a folder containing fragment files. Fragments can be supplied as PDB or SDF but all of them must be placed into the same folder. Each fragment included into the frag_library directory will be inserted to the scaffold (or molecular core). The chemical bonding will take place between the atom of the scaffold selected with frag_core_atom and all non symmetric hydrogen atoms found in each fragment. We can also fix the hydrogen atom of the fragment we want to connect setting the parameter called fragment_atom.

  • Type: String

  • Default: None

Note

There is an alternative method to run fragPELE. Instead of supplying a fragment library, we can supply an SDF containing fully grown ligands, with a parameter called frag_ligands.

Note

Note that frag_ligands and frag_library parameters cannot be defined simultaneously.

See also

frag_core, chain_core, frag_ligands, frag_core_atom, fragment_atom, Example 2, Example 3

frag_core_atom

  • Description: Defines which is the atom of the scaffold the fragments must be connected to when using fragment libraries (frag_library parameter).

  • Type: Two atoms, String-String, where each string corresponds to the name of one atom of the scaffold.

    • First atom: heavy atom connected to the hydrogen atom that will be replaced with each fragment.

    • Second atom: hydrogen atom to replace.

  • Default: None

Note

Note that this parameter only has an effect when a fragment library is supplied through the frag_library parameter.

Note

It is a mandatory parameter for fragPELE when a fragment library is supplied.

See also

frag_library, Example 2, Example 3

fragment_atom

  • Description: Defines which is the atom of each fragment the scaffold must be connected to when using fragment libraries (frag_library parameter).

  • Type: One atom, String, hydrogen atom to remove and replace with the scaffold.

  • Default: None

Warning

When fragment_atom is specified, all fragments from the library must contain one hydrogen atom that matches with that name. Then, the connection to the scaffold will be applied through that position. This strategy requires a manual selection of each attachment atom and the assignment of the right PDB atom name to it.

Note

Note that this parameter only has an effect when a fragment library is supplied through the frag_library parameter.

Note

It is an optional parameter. When missing, bonding to the scaffold will take place through all asymmetric hydrogen atoms.

See also

frag_library, Example 3

growing_steps

  • Description: Sets the number of growing steps to apply during the growth of the fragment.

  • Type: Integer

  • Default: 6

Note

Increasing the number of growing steps will smooth the alchemical change during the growth of the fragment but the simulation will become more expensive.

See also

steps_in_gs, sampling_steps, Example 3

steps_in_gs

  • Description: Sets the number of PELE steps to perform at each growing step.

  • Type: Integer

  • Default: 3

Note

Increasing the number of growing steps will promote the conformational sampling and reallocation of the ligand and its neighboring side chains but the simulation will become more expensive.

See also

growing_steps, sampling_steps, Example 3

sampling_steps

  • Description: Sets the number of PELE steps to perform during the final equilibration stage, which happens once the fragment is fully grown.

  • Type: Integer

  • Default: 20

Note

Increasing the number of equilibration steps will promote the conformational sampling and reallocation of the ligand and its neighboring side chains but the simulation will become more expensive.

See also

growing_steps, steps_in_gs, Example 3

pele_control_file

  • Description: Sets a custom control file template for PELE that will replace the predefined template that fragPELE uses.

  • Type: str

  • Default: None

Note

The template must have certain parameters assigned through predetermined flags (marked with the dollar symbol: $) so fragPELE can change them dynamically. Check an example of a template here: pele_template.conf

See also

Example 5

Example 1

In this example we set up a fragPELE simulation with 30 computation cores. The goal is to take the initial structure supplied with the frag_core parameter and alchemically convert it to molecules defined with the frag_ligands parameter.

# Required parameters
frag_core: "complex_with_scaffold.pdb"
chain_core: "L"
resname: "LIG"

# General parameters
cpus: 30
seed: 2021

# fragPELE parameters
frag_ligands: "fully_grown_ligands.sdf"

Example 2

In this example we set up a fragPELE simulation with 30 computation cores. The goal is to take the initial structure supplied with the frag_core parameter and alchemically attach all fragments defined in the library files from the path set by the frag_library parameter. We must also specify the atom of the scaffold where fragments need to be inserted using frag_core_atom parameter. In this case, we attach fragments through a hydrogen atom called H6 that is connected to a carbon atom with name C6. Fragments will be connected to this position through all asymmetric hydrogen atoms.

# Required parameters
frag_core: "complex_with_scaffold.pdb"
chain_core: "L"
resname: "LIG"

# General parameters
cpus: 30
seed: 2021

# fragPELE parameters
frag_library: "path/to/frag/libraries"
frag_core_atom: "C6-H6"

Example 3

In this example we set up a fragPELE simulation with 30 computation cores. The goal is to take the initial structure supplied with the frag_core parameter and alchemically attach all fragments defined in the library files from the path set by the frag_library parameter. We must also specify the atom of the scaffold where fragments need to be inserted using frag_core_atom parameter. In this case, we attach fragments through a hydrogen atom called H6 that is connected to a carbon atom with name C6. Since we also supply the fragment_atom parameter, fragments will be connected to atom C6 from scaffold through the hydrogen atom called HGRW.

# Required parameters
frag_core: "complex_with_scaffold.pdb"
chain_core: "L"
resname: "LIG"

# General parameters
cpus: 30
seed: 2021

# fragPELE parameters
frag_library: "path/to/frag/libraries"
frag_core_atom: "C6-H6"
fragment_atom: "HGRW"

Example 4

In this example we set up a fragPELE simulation with 30 computation cores. The goal is to take the initial structure supplied with the frag_core parameter and alchemically convert it to molecules defined with the frag_ligands parameter. Besides, we are significantly increasing the length of the alchemical growth because we ask for more growing steps (growing_steps) and more PELE steps per growing step (steps_in_gs). On the other hand, we reduce the length of the final equilibration (sampling_steps).

# Required parameters
frag_core: "complex_with_scaffold.pdb"
chain_core: "L"
resname: "LIG"

# General parameters
cpus: 30
seed: 2021

# fragPELE parameters
frag_ligands: "fully_grown_ligands.sdf"
growing_steps: 10
steps_in_gs: 5
sampling_steps: 10

Example 5

In this example we set up a fragPELE simulation with 48 computation cores. The goal is to take the initial structure supplied with the frag_core parameter and alchemically convert it to molecules defined with the frag_ligands parameter. Besides, we ask to use peleffy along with the Open Force Field parameters for hetero molecules with use_peleffy and forcefield parameters. Finally, we replace fragPELE’s default control file template with another template that we sett with pele_control_file.

# Required parameters
frag_core: "complex_with_scaffold.pdb"
chain_core: "L"
resname: "LIG"

# General parameters
cpus: 48
seed: 2022

# fragPELE parameters
frag_ligands: "fully_grown_ligands.sdf"
use_peleffy: True
forcefield: 'openff-2.0.0'
pele_control_file: "pele_template.conf"