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.

Attributes:

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

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.

Attributes:

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

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[CovalentInhibitorScanResult]

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	destination folder	None
max_credits	int | None	maximum credits for the workflow	None
webhook_url	str | None	URL that Rowan will POST to when the workflow completes	None
is_draft	bool	save as a draft without starting execution	False

Returns:

Type	Description
Workflow[CovalentInhibitorScanResult]	submitted workflow

Raises:

Type	Description
HTTPStatusError	request to the API fails