diff --git a/modules/mol/alg/pymod/ligand_scoring_base.py b/modules/mol/alg/pymod/ligand_scoring_base.py
index 577bbc77a815466857aca32655e8ee5d9a2ac961..de62916b9eb209e8a00830ab550929a500cb13d5 100644
--- a/modules/mol/alg/pymod/ligand_scoring_base.py
+++ b/modules/mol/alg/pymod/ligand_scoring_base.py
@@ -216,7 +216,7 @@ class LigandScorer:
self.max_symmetries = max_symmetries
# lazily computed attributes
- self._chain_mapper = None
+ self.__chain_mapper = None
# keep track of states
# simple integers instead of enums - documentation of property describes
@@ -364,7 +364,7 @@ class LigandScorer:
@property
- def chain_mapper(self):
+ def _chain_mapper(self):
""" Chain mapper object for the given :attr:`target`.
Can be used by child classes if needed, constructed with
@@ -372,12 +372,12 @@ class LigandScorer:
:type: :class:`ost.mol.alg.chain_mapping.ChainMapper`
"""
- if self._chain_mapper is None:
- self._chain_mapper = \
+ if self.__chain_mapper is None:
+ self.__chain_mapper = \
chain_mapping.ChainMapper(self.target,
n_max_naive=1e9,
resnum_alignments=self.resnum_alignments)
- return self._chain_mapper
+ return self.__chain_mapper
@staticmethod
def _extract_ligands(entity):
diff --git a/modules/mol/alg/pymod/ligand_scoring_lddtpli.py b/modules/mol/alg/pymod/ligand_scoring_lddtpli.py
index 5457a06c2a02d1d1dd197615c2b75c7c6413725e..4b2dfdcecfe39d3f76845d2e65344b75e784ea09 100644
--- a/modules/mol/alg/pymod/ligand_scoring_lddtpli.py
+++ b/modules/mol/alg/pymod/ligand_scoring_lddtpli.py
@@ -10,12 +10,87 @@ from ost.mol.alg import chain_mapping
from ost.mol.alg import ligand_scoring_base
class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
+ """ :class:`LigandScorer` implementing lDDT-PLI.
+
+ lDDT-PLI is an lDDT score considering contacts between ligand and
+ receptor. Where receptor consists of protein and nucleic acid chains that
+ pass the criteria for :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.
+
+ Given a target/model ligand pair, all possible mappings of model chains
+ onto their chemically equivalent target chains are enumerated in order
+ to compute the best possible lDDT-PLI.
+
+ By default, classic lDDT is computed. That means, contacts within
+ *lddt_pli_radius* are identified in the target and checked if they're
+ conserved in the model. Added contacts are not penalized. That means if
+ the ligand is nicely placed in the correct pocket, but that pocket now
+ suddenly interacts with MORE residues in the model, you still get a high
+ score. You can penalize for these added contacts with the
+ *add_mdl_contacts* flag. This additionally considers contacts within
+ *lddt_pli_radius* in the model but only if the involved atoms can
+ be mapped to the target. This is a requirement to 1) extract the respective
+ reference distance from the target 2) avoid usage of contacts for which
+ we have no experimental evidence. One special case are
+ contacts from chains that are NOT mapped to the target binding site. It is
+ very well possible that we have experimental evidence for this chain though
+ its just too far away from the target binding site.
+ We therefore try to map these contacts to the chain in the target with
+ equivalent sequence that is closest to the target binding site. If the
+ respective atoms can be mapped there, the contact is considered not
+ fulfilled and added as penalty.
+
+ :param model: Passed to parent constructor - see :class:`LigandScorer`.
+ :type model: :class:`ost.mol.EntityHandle`/:class:`ost.mol.EntityView`
+ :param target: Passed to parent constructor - see :class:`LigandScorer`.
+ :type target: :class:`ost.mol.EntityHandle`/:class:`ost.mol.EntityView`
+ :param model_ligands: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type model_ligands: :class:`list`
+ :param target_ligands: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type target_ligands: :class:`list`
+ :param resnum_alignments: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type resnum_alignments: :class:`bool`
+ :param rename_ligand_chain: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type rename_ligand_chain: :class:`bool`
+ :param substructure_match: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type substructure_match: :class:`bool`
+ :param coverage_delta: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type coverage_delta: :class:`float`
+ :param max_symmetries: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type max_symmetries: :class:`int`
+ :param check_resnames: On by default. Enforces residue name matches
+ between mapped model and target residues.
+ :type check_resnames: :class:`bool`
+ :param lddt_pli_radius: lDDT inclusion radius for lDDT-PLI.
+ :type lddt_pli_radius: :class:`float`
+ :param add_mdl_contacts: Whether to add mdl contacts.
+ :type add_mdl_contacts: :class:`bool`
+ :param lddt_pli_thresholds: Distance difference thresholds for lDDT.
+ :type lddt_pli_thresholds: :class:`list` of :class:`float`
+ :param lddt_pli_binding_site_radius: Pro param - dont use. Providing a value
+ Restores behaviour from previous
+ implementation that first extracted a
+ binding site with strict distance
+ threshold and computed lDDT-PLI only on
+ those target residues whereas the
+ current implementation includes every
+ atom within *lddt_pli_radius*.
+ :type lddt_pli_binding_site_radius: :class:`float`
+ """
def __init__(self, model, target, model_ligands=None, target_ligands=None,
resnum_alignments=False, rename_ligand_chain=False,
substructure_match=False, coverage_delta=0.2,
max_symmetries=1e5, check_resnames=True, lddt_pli_radius=6.0,
- add_mdl_contacts=True,
+ add_mdl_contacts=False,
lddt_pli_thresholds = [0.5, 1.0, 2.0, 4.0],
lddt_pli_binding_site_radius=None):
@@ -341,9 +416,9 @@ class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
mdl_center = mdl_ch_view.geometric_center
closest_ch = None
closest_dist = None
- for trg_ch in self.chain_mapper.chem_groups[chem_group_idx]:
+ for trg_ch in self._chain_mapper.chem_groups[chem_group_idx]:
if trg_ch not in lddt_chain_mapping.values():
- c = self.chain_mapper.target.FindChain(trg_ch).geometric_center
+ c = self._chain_mapper.target.FindChain(trg_ch).geometric_center
d = geom.Distance(mdl_center, c)
if closest_dist is None or d < closest_dist:
closest_dist = d
@@ -664,7 +739,7 @@ class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
def _lddt_pli_get_trg_data(self, target_ligand, max_r = None):
if target_ligand not in self._lddt_pli_target_data:
- trg = self.chain_mapper.target
+ trg = self._chain_mapper.target
if max_r is None:
max_r = self.lddt_pli_radius + max(self.lddt_pli_thresholds)
@@ -711,7 +786,7 @@ class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
inclusion_radius = self.lddt_pli_radius)
chem_groups = list()
- for g in self.chain_mapper.chem_groups:
+ for g in self._chain_mapper.chem_groups:
chem_groups.append([x for x in g if x in trg_chains])
self._lddt_pli_target_data[target_ligand] = (trg_residues,
@@ -733,7 +808,7 @@ class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
ref_bs_chain = ref_bs.FindChain(ref_ch)
query = "cname=" + mol.QueryQuoteName(ref_ch)
- ref_view = self.chain_mapper.target.Select(query)
+ ref_view = self._chain_mapper.target.Select(query)
for mdl_ch in mdl_chem_group:
aln = self._ref_mdl_alns[(ref_ch, mdl_ch)]
@@ -786,7 +861,7 @@ class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
self.__mappable_atoms = dict()
for (ref_cname, mdl_cname), aln in self._ref_mdl_alns.items():
self._mappable_atoms[(ref_cname, mdl_cname)] = set()
- ref_ch = self.chain_mapper.target.Select(f"cname={mol.QueryQuoteName(ref_cname)}")
+ ref_ch = self._chain_mapper.target.Select(f"cname={mol.QueryQuoteName(ref_cname)}")
mdl_ch = self._chain_mapping_mdl.Select(f"cname={mol.QueryQuoteName(mdl_cname)}")
aln.AttachView(0, ref_ch)
aln.AttachView(1, mdl_ch)
@@ -807,7 +882,7 @@ class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
if self.__chem_mapping is None:
self.__chem_mapping, self.__chem_group_alns, \
self.__chain_mapping_mdl = \
- self.chain_mapper.GetChemMapping(self.model)
+ self._chain_mapper.GetChemMapping(self.model)
return self.__chem_mapping
@property
@@ -815,15 +890,15 @@ class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
if self.__chem_group_alns is None:
self.__chem_mapping, self.__chem_group_alns, \
self.__chain_mapping_mdl = \
- self.chain_mapper.GetChemMapping(self.model)
+ self._chain_mapper.GetChemMapping(self.model)
return self.__chem_group_alns
@property
def _ref_mdl_alns(self):
if self.__ref_mdl_alns is None:
self.__ref_mdl_alns = \
- chain_mapping._GetRefMdlAlns(self.chain_mapper.chem_groups,
- self.chain_mapper.chem_group_alignments,
+ chain_mapping._GetRefMdlAlns(self._chain_mapper.chem_groups,
+ self._chain_mapper.chem_group_alignments,
self._chem_mapping,
self._chem_group_alns)
return self.__ref_mdl_alns
@@ -833,5 +908,5 @@ class LDDTPLIScorer(ligand_scoring_base.LigandScorer):
if self.__chain_mapping_mdl is None:
self.__chem_mapping, self.__chem_group_alns, \
self.__chain_mapping_mdl = \
- self.chain_mapper.GetChemMapping(self.model)
+ self._chain_mapper.GetChemMapping(self.model)
return self.__chain_mapping_mdl
diff --git a/modules/mol/alg/pymod/ligand_scoring_scrmsd.py b/modules/mol/alg/pymod/ligand_scoring_scrmsd.py
index 134821de9d9b3bfdf12f4e109e41bba087b6a06c..55c64899ecc951ac47ca684ef9038f2013c3a81b 100644
--- a/modules/mol/alg/pymod/ligand_scoring_scrmsd.py
+++ b/modules/mol/alg/pymod/ligand_scoring_scrmsd.py
@@ -7,7 +7,79 @@ from ost import mol
from ost.mol.alg import ligand_scoring_base
class SCRMSDScorer(ligand_scoring_base.LigandScorer):
-
+ """ :class:`LigandScorer` implementing symmetry corrected RMSD.
+
+ The symmetry corrected RMSD is computed based on a binding site
+ superposition.
+ The binding site is defined as all residues with at least one atom within
+ *bs_radius* around the target ligand in the target structure.
+ It only contains protein and nucleic acid residues from 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.
+
+ The respective model binding site for superposition is identified by
+ naively enumerating all possible mappings of model chains onto their
+ chemically equivalent target counterparts from the target binding site.
+ The *binding_sites_topn* with respect to lDDT score
+ are evaluated and the best resulting SCRMSD is returned. You can either
+ try to map ALL model chains onto the target binding site by enabling
+ *full_bs_search* or restrict the model chains for a specific target/model
+ ligand pair to the chains with at least one atom within *model_bs_radius*
+ around the model ligand. The latter can be significantly faster in case
+ of large complexes.
+
+ :param model: Passed to parent constructor - see :class:`LigandScorer`.
+ :type model: :class:`ost.mol.EntityHandle`/:class:`ost.mol.EntityView`
+ :param target: Passed to parent constructor - see :class:`LigandScorer`.
+ :type target: :class:`ost.mol.EntityHandle`/:class:`ost.mol.EntityView`
+ :param model_ligands: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type model_ligands: :class:`list`
+ :param target_ligands: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type target_ligands: :class:`list`
+ :param resnum_alignments: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type resnum_alignments: :class:`bool`
+ :param rename_ligand_chain: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type rename_ligand_chain: :class:`bool`
+ :param substructure_match: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type substructure_match: :class:`bool`
+ :param coverage_delta: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type coverage_delta: :class:`float`
+ :param max_symmetries: Passed to parent constructor - see
+ :class:`LigandScorer`.
+ :type max_symmetries: :class:`int`
+ :param bs_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 bs_radius: :class:`float`
+ :param lddt_lp_radius: lDDT inclusion radius for lDDT-LP.
+ :type lddt_lp_radius: :class:`float`
+ :param model_bs_radius: inclusion radius for model binding sites.
+ Only used when full_bs_search=False, otherwise the
+ radius is effectively infinite. Only chains with
+ atoms within this distance of a model ligand will
+ be considered in the chain mapping.
+ :type model_bs_radius: :class:`float`
+ :param binding_sites_topn: maximum number of model binding site
+ representations to assess per target binding
+ site.
+ :type binding_sites_topn: :class:`int`
+ :param full_bs_search: If True, all potential binding sites in the model
+ are searched for each target binding site. If False,
+ the search space in the model is reduced to chains
+ around (`model_bs_radius` Å) model ligands.
+ This speeds up computations, but may result in
+ ligands not being scored if the predicted ligand
+ pose is too far from the actual binding site.
+ :type full_bs_search: :class:`bool`
+ """
def __init__(self, model, target, model_ligands=None, target_ligands=None,
resnum_alignments=False, rename_ligand_chain=False,
substructure_match=False, coverage_delta=0.2,
@@ -105,11 +177,11 @@ class SCRMSDScorer(ligand_scoring_base.LigandScorer):
if key not in self._repr:
ref_bs = self._get_target_binding_site(target_ligand)
if self.full_bs_search:
- reprs = self.chain_mapper.GetRepr(
+ reprs = self._chain_mapper.GetRepr(
ref_bs, self.model, inclusion_radius=self.lddt_lp_radius,
topn=self.binding_sites_topn)
else:
- reprs = self.chain_mapper.GetRepr(ref_bs, self.model,
+ reprs = self._chain_mapper.GetRepr(ref_bs, self.model,
inclusion_radius=self.lddt_lp_radius,
topn=self.binding_sites_topn,
chem_mapping_result = self._get_get_repr_input(model_ligand))
@@ -139,7 +211,7 @@ class SCRMSDScorer(ligand_scoring_base.LigandScorer):
h = ref_res.handle.GetHashCode()
if h not in ref_residues_hashes and \
h not in ignored_residue_hashes:
- if self.chain_mapper.target.ViewForHandle(ref_res).IsValid():
+ if self._chain_mapper.target.ViewForHandle(ref_res).IsValid():
h = ref_res.handle.GetHashCode()
ref_residues_hashes.add(h)
elif ref_res.is_ligand:
@@ -179,7 +251,7 @@ class SCRMSDScorer(ligand_scoring_base.LigandScorer):
if self.__chem_mapping is None:
self.__chem_mapping, self.__chem_group_alns, \
self.__chain_mapping_mdl = \
- self.chain_mapper.GetChemMapping(self.model)
+ self._chain_mapper.GetChemMapping(self.model)
return self.__chem_mapping
@property
@@ -187,15 +259,15 @@ class SCRMSDScorer(ligand_scoring_base.LigandScorer):
if self.__chem_group_alns is None:
self.__chem_mapping, self.__chem_group_alns, \
self.__chain_mapping_mdl = \
- self.chain_mapper.GetChemMapping(self.model)
+ self._chain_mapper.GetChemMapping(self.model)
return self.__chem_group_alns
@property
def _ref_mdl_alns(self):
if self.__ref_mdl_alns is None:
self.__ref_mdl_alns = \
- chain_mapping._GetRefMdlAlns(self.chain_mapper.chem_groups,
- self.chain_mapper.chem_group_alignments,
+ chain_mapping._GetRefMdlAlns(self._chain_mapper.chem_groups,
+ self._chain_mapper.chem_group_alignments,
self._chem_mapping,
self._chem_group_alns)
return self.__ref_mdl_alns
@@ -205,7 +277,7 @@ class SCRMSDScorer(ligand_scoring_base.LigandScorer):
if self.__chain_mapping_mdl is None:
self.__chem_mapping, self.__chem_group_alns, \
self.__chain_mapping_mdl = \
- self.chain_mapper.GetChemMapping(self.model)
+ self._chain_mapper.GetChemMapping(self.model)
return self.__chain_mapping_mdl
def _get_get_repr_input(self, mdl_ligand):