Covalent Inhibitor Scan

Beta

This workflow is in beta. Its interface and behavior may change.

Covalent inhibitor scan workflow - reactivity profile via ML/MM umbrella sampling.

CovalentInhibitorScanPoint dataclass

CovalentInhibitorScanPoint(
    index: int,
    distance: float,
    force_constant: float,
    free_energy: float | None,
    mean_distance: float | None,
    n_samples: int,
    molecule: Molecule | None,
)

A point on the covalent inhibitor reactivity profile.

Parameters:

Name	Type	Description	Default
index	int	window index.	required
distance	float	bias center for this window, in Å.	required
force_constant	float	harmonic bias force constant, in kcal/mol/Ų.	required
free_energy	float | None	unbiased free energy at this center, in kcal/mol, if available.	required
mean_distance	float | None	mean sampled reactive-bond distance, in Å, if available.	required
n_samples	int	production samples contributing to this window.	required
molecule	Molecule | None	final sampled geometry of the model region, if available.	required

UmbrellaSamplingConvergence dataclass

UmbrellaSamplingConvergence(
    overlap_matrix: tuple[tuple[float, ...], ...],
    round_trips: int,
    worst_pair_acceptance: float | None,
)

Diagnostics saying whether a reactivity profile can be trusted.

Parameters:

Name	Type	Description	Default
overlap_matrix	tuple[tuple[float, ...], ...]	MBAR overlap between windows; low overlap between neighbours means the profile should not be trusted.	required
round_trips	int	replicas that traversed the whole coordinate and returned.	required
worst_pair_acceptance	float | None	lowest exchange acceptance over neighbouring pairs, if available.	required

CovalentInhibitorScanResult dataclass

CovalentInhibitorScanResult(
    workflow_data: dict[str, Any],
    workflow_type: str,
    workflow_uuid: str,
    complete: bool = True,
)

Bases: WorkflowResult

Result from a covalent inhibitor scan workflow.

points property

points: list[CovalentInhibitorScanPoint]

Points on the reactivity profile, in window-index order.

convergence property

convergence: UmbrellaSamplingConvergence | None

Sampling convergence diagnostics, when available.

barrier property

barrier: float | None

Activation free energy for addition, in kcal/mol, or None without an interior maximum.

get_energies

get_energies() -> list[tuple[float, float | None]]

Get bias-center distances paired with free energies.

Returns:

Type	Description
list[tuple[float, float | None]]	List of (distance, free_energy) tuples, in Å and kcal/mol respectively.

submit_covalent_inhibitor_scan_workflow

submit_covalent_inhibitor_scan_workflow(
    protein: Protein | ProteinUUID,
    protein_reactive_atom_index: int,
    ligand_reactive_atom_index: int,
    reactant_smiles: str,
    settings: UmbrellaSamplingScanSettings | None = None,
    name: str = "Covalent Inhibitor Scan Workflow",
    folder_uuid: str | None = None,
    folder: Folder | None = None,
    max_credits: int | None = None,
    webhook_url: str | None = None,
    is_draft: bool = False,
) -> Workflow

Submits a covalent inhibitor scan workflow to the API.

.. warning:: This workflow is in beta. Its interface and behavior may change.

Seeds windows along the reactive bond distance with a steered pull, samples them via ML/MM umbrella sampling, and combines them into a free energy profile.

Parameters:

Name	Type	Description	Default
protein	Protein | ProteinUUID	covalently docked protein-ligand complex (protein plus the ligand as a non-polymer residue). Can be a UUID or a Protein object.	required
protein_reactive_atom_index	int	0-based index of the reacting protein atom, in PDB record order.	required
ligand_reactive_atom_index	int	0-based index of the reacting ligand atom, in PDB record order.	required
reactant_smiles	str	SMILES of the neutral reactant ligand, used to rebuild the ligand as a separate non-covalent molecule at the MM level.	required
settings	UmbrellaSamplingScanSettings | None	settings controlling the umbrella sampling. Defaults to stjames.UmbrellaSamplingScanSettings().	None
name	str	name of the workflow.	'Covalent Inhibitor Scan Workflow'
folder_uuid	str | None	UUID of the folder to place the workflow in.	None
folder	Folder | None	Folder object to store the workflow in.	None
max_credits	int | None	maximum number of credits to use for the workflow.	None
webhook_url	str | None	URL that Rowan will POST to when the workflow completes.	None
is_draft	bool	if True, submit the workflow as a draft without starting execution.	False

Returns:

Type	Description
Workflow	Workflow object representing the submitted workflow.

Raises:

Type	Description
requests.HTTPError	if the request to the API fails.