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OpenStructure
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Public Member Functions | |
| def | __init__ |
| def | chain_mapper |
| def | rmsd_matrix |
| def | lddt_pli_matrix |
| def | coverage_matrix |
| def | rmsd |
| def | rmsd_details |
| def | lddt_pli |
| def | lddt_pli_details |
| def | unassigned_target_ligands |
| def | unassigned_target_ligand_descriptions |
| def | unassigned_model_ligands |
| def | unassigned_model_ligand_descriptions |
Scorer class to compute various small molecule ligand (non polymer) scores.
.. note ::
Extra requirements:
- Python modules `numpy` and `networkx` must be available
(e.g. use ``pip install numpy networkx``)
At the moment, two scores are available:
* lDDT-PLI, that looks at the conservation of protein-ligand contacts
with :class:`lDDT <ost.mol.alg.lddt.lDDTScorer>`.
* Binding-site superposed, symmetry-corrected RMSD that assesses the
accuracy of the ligand pose (BiSyRMSD, hereinafter referred to as RMSD).
Both scores involve local chain mapping of the reference binding site
onto the model, symmetry-correction, and finally assignment (mapping)
of model and target ligands, as described in (Manuscript in preparation).
The binding site is defined based on a radius around the target ligand
in the reference structure only. It only contains protein and nucleic
acid chains that pass the criteria for the
:class:`chain mapping <ost.mol.alg.chain_mapping>`. This means ignoring
other ligands, waters, short polymers as well as any incorrectly connected
chains that may be in proximity.
Results are available as matrices (`(lddt_pli|rmsd)_matrix`), where every
target-model score is reported in a matrix; as `(lddt_pli|rmsd)` where
a model-target assignment has been determined (see below) and reported in
a dictionary; and as (`(lddt_pli|rmsd)_details`) methods, which report
additional details about different aspects of the scoring such as chain
mapping.
The behavior of chain mapping and ligand assignment can be controlled
with the `global_chain_mapping` and `rmsd_assignment` arguments.
By default, chain mapping is performed locally, ie. only within the
binding site. As a result, different ligand scores can correspond to
different chain mappings. This tends to produce more favorable scores,
especially in large, partially regular oligomeric complexes.
Setting `global_chain_mapping=True` enforces a single global chain mapping,
as per :meth:`ost.mol.alg.chain_mapping.ChainMapper.GetMapping`.
Note that this global chain mapping currently ignores non polymer entities
such as small ligands, and may result in overly pessimistic scores.
By default, target-model ligand assignments are computed independently
for the RMSD and lDDT-PLI scores. For RMSD, each model ligand is uniquely
assigned to a target ligand, starting from the "best" possible mapping
(lowest RMSD) and using each target and model ligand in a single
assignment. Ties are resolved by best (highest) lDDT-PLI. Similarly,
for lDDT-PLI, the assignment is based on the highest lDDT-PLI, and ties
broken by lowest RMSD. Setting `rmsd_assignment=True` forces a single
ligand assignment, based on RMSD only. Ties are broken arbitrarily.
By default, only exact matches between target and model ligands are
considered. This is a problem when the target only contains a subset
of the expected atoms (for instance if atoms are missing in an
experimental structure, which often happens in the PDB). With
`substructure_match=True`, complete model ligands can be scored against
partial target ligands. One problem with this approach is that it is
very easy to find good matches to small, irrelevant ligands like EDO, CO2
or GOL. To counter that, the assignment algorithm considers the coverage,
expressed as the fraction of atoms of the model ligand atoms covered in the
target. Higher coverage matches are prioritized, but a match with a better
score will be preferred if it falls within a window of `coverage_delta`
(by default 0.2) of a worse-scoring match. As a result, for instance,
with a delta of 0.2, a low-score match with coverage 0.96 would be
preferred to a high-score match with coverage 0.90.
Assumptions:
The class generally assumes that the
:attr:`~ost.mol.ResidueHandle.is_ligand` property is properly set on all
the ligand atoms, and only ligand atoms. This is typically the case for
entities loaded from mmCIF (tested with mmCIF files from the PDB and
SWISS-MODEL). Legacy PDB files must contain `HET` headers (which is usually
the case for files downloaded from the PDB but not elsewhere).
The class doesn't perform any cleanup of the provided structures.
It is up to the caller to ensure that the data is clean and suitable for
scoring. :ref:`Molck <molck>` should be used with extra
care, as many of the options (such as `rm_non_std` or `map_nonstd_res`) can
cause ligands to be removed from the structure. If cleanup with Molck is
needed, ligands should be kept aside and passed separately. Non-ligand residues
should be valid compounds with atom names following the naming conventions
of the component dictionary. Non-standard residues are acceptable, and if
the model contains a standard residue at that position, only atoms with
matching names will be considered.
Unlike most of OpenStructure, this class does not assume that the ligands
(either in the model or the target) are part of the PDB component
dictionary. They may have arbitrary residue names. Residue names do not
have to match between the model and the target. Matching is based on
the calculation of isomorphisms which depend on the atom element name and
atom connectivity (bond order is ignored).
It is up to the caller to ensure that the connectivity of atoms is properly
set before passing any ligands to this class. Ligands with improper
connectivity will lead to bogus results.
Note, however, that atom names should be unique within a residue (ie two
distinct atoms cannot have the same atom name).
This only applies to the ligand. The rest of the model and target
structures (protein, nucleic acids) must still follow the usual rules and
contain only residues from the compound library.
Although it isn't a requirement, hydrogen atoms should be removed from the
structures. Here is an example code snippet that will perform a reasonable
cleanup. Keep in mind that this is most likely not going to work as
expected with entities loaded from PDB files, as the `is_ligand` flag is
probably not set properly.
Here is a snippet example of how to use this code::
from ost.mol.alg.ligand_scoring import LigandScorer
from ost.mol.alg import Molck, MolckSettings
# Load data
# Structure model in PDB format, containing the receptor only
model = io.LoadPDB("path_to_model.pdb")
# Ligand model as SDF file
model_ligand = io.LoadEntity("path_to_ligand.sdf", format="sdf")
# Target loaded from mmCIF, containing the ligand
target = io.LoadMMCIF("path_to_target.cif")
# Cleanup a copy of the structures
cleaned_model = model.Copy()
cleaned_target = target.Copy()
molck_settings = MolckSettings(rm_unk_atoms=True,
rm_non_std=False,
rm_hyd_atoms=True,
rm_oxt_atoms=False,
rm_zero_occ_atoms=False,
colored=False,
map_nonstd_res=False,
assign_elem=True)
Molck(cleaned_model, conop.GetDefaultLib(), molck_settings)
Molck(cleaned_target, conop.GetDefaultLib(), molck_settings)
# Setup scorer object and compute lDDT-PLI
model_ligands = [model_ligand.Select("ele != H")]
ls = LigandScorer(model=cleaned_model, target=cleaned_target, model_ligands=model_ligands)
print("lDDT-PLI:", ls.lddt_pli)
print("RMSD:", ls.rmsd)
:param model: Model structure - a deep copy is available as :attr:`model`.
No additional processing (ie. Molck), checks,
stereochemistry checks or sanitization is performed on the
input. Hydrogen atoms are kept.
:type model: :class:`ost.mol.EntityHandle`/:class:`ost.mol.EntityView`
:param target: Target structure - a deep copy is available as :attr:`target`.
No additional processing (ie. Molck), checks or sanitization
is performed on the input. Hydrogen atoms are kept.
:type target: :class:`ost.mol.EntityHandle`/:class:`ost.mol.EntityView`
:param model_ligands: Model ligands, as a list of
:class:`~ost.mol.ResidueHandle` belonging to the model
entity. Can be instantiated with either a :class:list of
:class:`~ost.mol.ResidueHandle`/:class:`ost.mol.ResidueView`
or of :class:`ost.mol.EntityHandle`/:class:`ost.mol.EntityView`.
If `None`, ligands will be extracted based on the
:attr:`~ost.mol.ResidueHandle.is_ligand` flag (this is
normally set properly in entities loaded from mmCIF).
:type model_ligands: :class:`list`
:param target_ligands: Target ligands, as a list of
:class:`~ost.mol.ResidueHandle` belonging to the target
entity. Can be instantiated either a :class:list of
:class:`~ost.mol.ResidueHandle`/:class:`ost.mol.ResidueView`
or of :class:`ost.mol.EntityHandle`/:class:`ost.mol.EntityView`
containing a single residue each.
If `None`, ligands will be extracted based on the
:attr:`~ost.mol.ResidueHandle.is_ligand` flag (this is
normally set properly in entities loaded from mmCIF).
:type target_ligands: :class:`list`
:param resnum_alignments: Whether alignments between chemically equivalent
chains in *model* and *target* can be computed
based on residue numbers. This can be assumed in
benchmarking setups such as CAMEO/CASP.
:type resnum_alignments: :class:`bool`
:param check_resnames: On by default. Enforces residue name matches
between mapped model and target residues.
:type check_resnames: :class:`bool`
:param rename_ligand_chain: If a residue with the same chain name and
residue number than an explicitly passed model
or target ligand exits in the structure,
and `rename_ligand_chain` is False, a
RuntimeError will be raised. If
`rename_ligand_chain` is True, the ligand will
be moved to a new chain instead, and the move
will be logged to the console with SCRIPT
level.
:type rename_ligand_chain: :class:`bool`
:param chain_mapper: a chain mapper initialized for the target structure.
If None (default), a chain mapper will be initialized
lazily as required.
:type chain_mapper: :class:`ost.mol.alg.chain_mapping.ChainMapper`
:param substructure_match: Set this to True to allow partial target ligand.
:type substructure_match: :class:`bool`
:param coverage_delta: the coverage delta for partial ligand assignment.
:type coverage_delta: :class:`float`
:param radius: Inclusion radius for the binding site. Residues with
atoms within this distance of the ligand will be considered
for inclusion in the binding site.
:type radius: :class:`float`
:param lddt_pli_radius: lDDT inclusion radius for lDDT-PLI.
:type lddt_pli_radius: :class:`float`
:param lddt_lp_radius: lDDT inclusion radius for lDDT-LP.
:type lddt_lp_radius: :class:`float`
:param binding_sites_topn: maximum number of target binding site
representations to assess, per target ligand.
Ignored if `global_chain_mapping` is True.
:type binding_sites_topn: :class:`int`
:param global_chain_mapping: set to True to use a global chain mapping for
the polymer (protein, nucleotide) chains.
Defaults to False, in which case only local
chain mappings are allowed (where different
ligand may be scored against different chain
mappings).
:type global_chain_mapping: :class:`bool`
:param custom_mapping: Provide custom chain mapping between *model* and
*target* that is used as global chain mapping.
Dictionary with target chain names as key and model
chain names as value. Only has an effect if
*global_chain_mapping* is True.
:type custom_mapping: :class:`dict`
:param rmsd_assignment: assign ligands based on RMSD only. The default
(False) is to use a combination of lDDT-PLI and
RMSD for the assignment.
:type rmsd_assignment: :class:`bool`
:param n_max_naive: Parameter for global chain mapping. If *model* and
*target* have less or equal that number of chains,
the full
mapping solution space is enumerated to find the
the optimum. A heuristic is used otherwise.
:type n_max_naive: :class:`int`
:param max_symmetries: If more than that many isomorphisms exist for
a target-ligand pair, it will be ignored and reported
as unassigned.
:type max_symmetries: :class:`int`
:param unassigned: If True, unassigned model ligands are reported in
the output together with assigned ligands, with a score
of None, and reason for not being assigned in the
\\*_details matrix. Defaults to False.
:type unassigned: :class:`bool`
Definition at line 13 of file ligand_scoring.py.
| def __init__ | ( | self, | |
| model, | |||
| target, | |||
model_ligands = None, |
|||
target_ligands = None, |
|||
resnum_alignments = False, |
|||
check_resnames = True, |
|||
rename_ligand_chain = False, |
|||
chain_mapper = None, |
|||
substructure_match = False, |
|||
coverage_delta = 0.2, |
|||
radius = 4.0, |
|||
lddt_pli_radius = 6.0, |
|||
lddt_lp_radius = 10.0, |
|||
binding_sites_topn = 100000, |
|||
global_chain_mapping = False, |
|||
rmsd_assignment = False, |
|||
n_max_naive = 12, |
|||
max_symmetries = 1e5, |
|||
custom_mapping = None, |
|||
unassigned = False |
|||
| ) |
Definition at line 266 of file ligand_scoring.py.
| def chain_mapper | ( | self | ) |
Chain mapper object for the given :attr:`target`. :type: :class:`ost.mol.alg.chain_mapping.ChainMapper`
Definition at line 356 of file ligand_scoring.py.
| def coverage_matrix | ( | self | ) |
Get the matrix of model ligand atom coverage in the target. Target ligands are in rows, model ligands in columns. A value of 0 indicates that there was no isomorphism between the model and target ligands. If `substructure_match=False`, only full match isomorphisms are considered, and therefore only values of 1.0 and 0.0 are reported. :rtype: :class:`~numpy.ndarray`
Definition at line 1156 of file ligand_scoring.py.
| def lddt_pli | ( | self | ) |
Get a dictionary of lDDT-PLI score values, keyed by model ligand (chain name, :class:`~ost.mol.ResNum`). If the scoring object was instantiated with `unassigned=True`, some scores may be `None`. :rtype: :class:`dict`
Definition at line 1252 of file ligand_scoring.py.
| def lddt_pli_details | ( | self | ) |
Get a dictionary of lDDT-PLI score details (dictionaries), keyed by model ligand (chain name, :class:`~ost.mol.ResNum`). Each sub-dictionary contains the following information: * `lddt_pli`: the lDDT-PLI score value. * `rmsd`: the RMSD score value corresponding to the lDDT-PLI chain mapping and assignment. This may differ from the RMSD-based assignment. Note that a different isomorphism than `lddt_pli` may be used. * `lddt_lp`: the lDDT score of the ligand pocket (lDDT-LP). * `lddt_pli_n_contacts`: number of total contacts used in lDDT-PLI, summed over all thresholds. Can be divided by 8 to obtain the number of atomic contacts. * `bs_ref_res`: a list of residues (:class:`~ost.mol.ResidueHandle`) that define the binding site in the reference. * `bs_ref_res_mapped`: a list of residues (:class:`~ost.mol.ResidueHandle`) in the reference binding site that could be mapped to the model. * `bs_mdl_res_mapped`: a list of residues (:class:`~ost.mol.ResidueHandle`) in the model that were mapped to the reference binding site. The residues are in the same order as `bs_ref_res_mapped`. * `bb_rmsd`: the RMSD of the binding site backbone after superposition. Note: not used for lDDT-PLI computation. * `target_ligand`: residue handle of the target ligand. * `model_ligand`: residue handle of the model ligand. * `chain_mapping`: local chain mapping as a dictionary, with target chain name as key and model chain name as value. * `transform`: transformation to superpose the model onto the target (for RMSD only). * `substructure_match`: whether the score is the result of a partial (substructure) match. A value of `True` indicates that the target ligand covers only part of the model, while `False` indicates a perfect match. * `inconsistent_residues`: a list of tuples of mapped residues views (:class:`~ost.mol.ResidueView`) with residue names that differ between the reference and the model, respectively. The list is empty if all residue names match, which is guaranteed if `check_resnames=True`. Note: more binding site mappings may be explored during scoring, but only inconsistencies in the selected mapping are reported. * `unassigned`: only if the scorer was instantiated with `unassigned=True`: `False` If the scoring object was instantiated with `unassigned=True`, in addition the unmapped ligands will be reported with a score of `None` and the following information: * `unassigned`: `True`, * `reason_short`: a short token of the reason, see :attr:`unassigned_model_ligands` for details and meaning. * `reason_long`: a human-readable text of the reason, see :attr:`unassigned_model_ligands` for details and meaning. * `lddt_pli`: `None` :rtype: :class:`dict`
Definition at line 1269 of file ligand_scoring.py.
| def lddt_pli_matrix | ( | self | ) |
Get the matrix of lDDT-PLI values. Target ligands are in rows, model ligands in columns. NaN values indicate that no lDDT-PLI could be computed (i.e. different ligands). :rtype: :class:`~numpy.ndarray`
Definition at line 1133 of file ligand_scoring.py.
| def rmsd | ( | self | ) |
Get a dictionary of RMSD score values, keyed by model ligand (chain name, :class:`~ost.mol.ResNum`). If the scoring object was instantiated with `unassigned=True`, some scores may be `None`. :rtype: :class:`dict`
Definition at line 1173 of file ligand_scoring.py.
| def rmsd_details | ( | self | ) |
Get a dictionary of RMSD score details (dictionaries), keyed by model ligand (chain name, :class:`~ost.mol.ResNum`). The value is a dictionary. For ligands that were assigned (mapped) to the target, the dictionary contain the following information: * `rmsd`: the RMSD score value. * `lddt_lp`: the lDDT score of the ligand pocket (lDDT-LP). * `bs_ref_res`: a list of residues (:class:`~ost.mol.ResidueHandle`) that define the binding site in the reference. * `bs_ref_res_mapped`: a list of residues (:class:`~ost.mol.ResidueHandle`) in the reference binding site that could be mapped to the model. * `bs_mdl_res_mapped`: a list of residues (:class:`~ost.mol.ResidueHandle`) in the model that were mapped to the reference binding site. The residues are in the same order as `bs_ref_res_mapped`. * `bb_rmsd`: the RMSD of the binding site backbone after superposition * `target_ligand`: residue handle of the target ligand. * `model_ligand`: residue handle of the model ligand. * `chain_mapping`: local chain mapping as a dictionary, with target chain name as key and model chain name as value. * `transform`: transformation to superpose the model onto the target. * `substructure_match`: whether the score is the result of a partial (substructure) match. A value of `True` indicates that the target ligand covers only part of the model, while `False` indicates a perfect match. * `coverage`: the fraction of model atoms covered by the assigned target ligand, in the interval (0, 1]. If `substructure_match` is `False`, this will always be 1. * `inconsistent_residues`: a list of tuples of mapped residues views (:class:`~ost.mol.ResidueView`) with residue names that differ between the reference and the model, respectively. The list is empty if all residue names match, which is guaranteed if `check_resnames=True`. Note: more binding site mappings may be explored during scoring, but only inconsistencies in the selected mapping are reported. * `unassigned`: only if the scorer was instantiated with `unassigned=True`: `False` If the scoring object was instantiated with `unassigned=True`, in addition the unassigned ligands will be reported with a score of `None` and the following information: * `unassigned`: `True`, * `reason_short`: a short token of the reason, see :attr:`unassigned_model_ligands` for details and meaning. * `reason_long`: a human-readable text of the reason, see :attr:`unassigned_model_ligands` for details and meaning. * `rmsd`: `None` :rtype: :class:`dict`
Definition at line 1190 of file ligand_scoring.py.
| def rmsd_matrix | ( | self | ) |
Get the matrix of RMSD values. Target ligands are in rows, model ligands in columns. NaN values indicate that no RMSD could be computed (i.e. different ligands). :rtype: :class:`~numpy.ndarray`
Definition at line 1110 of file ligand_scoring.py.
| def unassigned_model_ligand_descriptions | ( | self | ) |
Get a human-readable description of why model ligands were unassigned, as a dictionary keyed by the controlled dictionary from :attr:`unassigned_model_ligands`.
Definition at line 1448 of file ligand_scoring.py.
| def unassigned_model_ligands | ( | self | ) |
Get a dictionary of model ligands not assigned to any target ligand, keyed by model ligand (chain name, :class:`~ost.mol.ResNum`). The assignment for the lDDT-PLI score is used (and is controlled by the `rmsd_assignment` argument). Each item contains a string from a controlled dictionary about the reason for the absence of assignment. A human-readable description can be obtained from the :attr:`unassigned_model_ligand_descriptions` property. Currently, the following reasons are reported: * `no_ligand`: there was no ligand in the target. * `disconnected`: the ligand graph is disconnected. * `binding_site`: a potential assignment was found in the target, but there were no polymer residues in proximity of the ligand in the target. * `model_representation`: a potential assignment was found in the target, but no representation of the binding site was found in the model. (I.e. the binding site was not modeled. Remember: the binding site is defined in the target structure, the position of the model ligand itself is ignored at this point.) * `identity`: the ligand was not found in the target (by graph isomorphism). Check your ligand connectivity, and enable the `substructure_match` option if the target ligand is incomplete. * `stoichiometry`: there was a possible assignment in the target, but the model target was already assigned to a different model ligand. This indicates different stoichiometries. * `symmetries`: too many symmetries were found (by graph isomorphisms). Increase `max_symmetries`. Some of these reasons can be overlapping, but a single reason will be reported. :rtype: :class:`dict`
Definition at line 1396 of file ligand_scoring.py.
| def unassigned_target_ligand_descriptions | ( | self | ) |
Get a human-readable description of why target ligands were unassigned, as a dictionary keyed by the controlled dictionary from :attr:`unassigned_target_ligands`.
Definition at line 1386 of file ligand_scoring.py.
| def unassigned_target_ligands | ( | self | ) |
Get a dictionary of target ligands not assigned to any model ligand, keyed by target ligand (chain name, :class:`~ost.mol.ResNum`). The assignment for the lDDT-PLI score is used (and is controlled by the `rmsd_assignment` argument). Each item contains a string from a controlled dictionary about the reason for the absence of assignment. A human-readable description can be obtained from the :attr:`unassigned_target_ligand_descriptions` property. Currently, the following reasons are reported: * `no_ligand`: there was no ligand in the model. * `disconnected`: the ligand graph was disconnected. * `binding_site`: no residues were in proximity of the ligand. * `model_representation`: no representation of the reference binding site was found in the model. (I.e. the binding site was not modeled. Remember: the binding site is defined in the target structure, the position of the model ligand itself is ignored at this point.) * `identity`: the ligand was not found in the model (by graph isomorphism). Check your ligand connectivity, and enable the `substructure_match` option if the target ligand is incomplete. * `stoichiometry`: there was a possible assignment in the model, but the model ligand was already assigned to a different target ligand. This indicates different stoichiometries. * `symmetries`: too many symmetries were found (by graph isomorphisms). Increase `max_symmetries`. Some of these reasons can be overlapping, but a single reason will be reported. :rtype: :class:`dict`
Definition at line 1336 of file ligand_scoring.py.
| binding_sites_topn |
Definition at line 312 of file ligand_scoring.py.
| check_resnames |
Definition at line 306 of file ligand_scoring.py.
| coverage_delta |
Definition at line 318 of file ligand_scoring.py.
| global_chain_mapping |
Definition at line 313 of file ligand_scoring.py.
| lddt_lp_radius |
Definition at line 311 of file ligand_scoring.py.
| lddt_pli_radius |
Definition at line 310 of file ligand_scoring.py.
| max_symmetries |
Definition at line 316 of file ligand_scoring.py.
| model |
Definition at line 269 of file ligand_scoring.py.
| model_ligands |
Definition at line 294 of file ligand_scoring.py.
| n_max_naive |
Definition at line 315 of file ligand_scoring.py.
| radius |
Definition at line 309 of file ligand_scoring.py.
| rename_ligand_chain |
Definition at line 307 of file ligand_scoring.py.
| resnum_alignments |
Definition at line 305 of file ligand_scoring.py.
| rmsd_assignment |
Definition at line 314 of file ligand_scoring.py.
| substructure_match |
Definition at line 308 of file ligand_scoring.py.
| target |
Definition at line 276 of file ligand_scoring.py.
| target_ligands |
Definition at line 284 of file ligand_scoring.py.
| unassigned |
Definition at line 317 of file ligand_scoring.py.
1.8.5