qsscore.py

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import itertools
import numpy as np
from scipy.spatial import distance
 
import time
from ost import mol
 
class QSEntity:
    """ Helper object for QS-score computation
 
    Holds structural information and getters for interacting chains, i.e.
    interfaces. Peptide residues are represented by their CB position
    (CA for GLY) and nucleotides by C3'.
 
    :param ent: Structure for QS score computation
    :type ent: :class:`ost.mol.EntityView`/:class:`ost.mol.EntityHandle`
    :param contact_d: Pairwise distance of residues to be considered as contacts
    :type contact_d: :class:`float`
    """
    def __init__(self, ent, contact_d = 12.0):
        pep_query = "(peptide=true and (aname=\"CB\" or (rname=\"GLY\" and aname=\"CA\")))"
        nuc_query = "(nucleotide=True and aname=\"C3'\")"
        self._view_view = ent.Select(" or ".join([pep_query, nuc_query]))
        self._contact_d_contact_d = contact_d
 
        # the following attributes will be lazily evaluated
        self._chain_names_chain_names = None
        self._interacting_chains_interacting_chains = None
        self._sequence_sequence = dict()
        self._pos_pos = dict()
        self._pair_dist_pair_dist = dict()
        # min and max xyz for elements in pos used for fast collision
        # detection
        self._min_pos_min_pos = dict()
        self._max_pos_max_pos = dict()
 
    @property
    def view(self):
        """ Processed structure
 
        View that only contains representative atoms. That's CB for peptide
        residues (CA for GLY) and C3' for nucleotides.
 
        :type: :class:`ost.mol.EntityView`
        """
        return self._view_view
 
    @property
    def contact_d(self):
        """ Pairwise distance of residues to be considered as contacts
 
        Given at :class:`QSEntity` construction
 
        :type: :class:`float`
        """
        return self._contact_d_contact_d
 
    @property
    def chain_names(self):
        """ Chain names in :attr:`~view`
 
        Names are sorted
 
        :type: :class:`list` of :class:`str`
        """
        if self._chain_names_chain_names is None:
            self._chain_names_chain_names = sorted([ch.name for ch in self.viewview.chains])
        return self._chain_names_chain_names
 
    @property
    def interacting_chains(self):
        """ Pairs of chains in :attr:`~view` with at least one contact
 
        :type: :class:`list` of :class:`tuples`
        """
        if self._interacting_chains_interacting_chains is None:            
            self._interacting_chains_interacting_chains = list()
            for x in itertools.combinations(self.chain_nameschain_names, 2):
                if self.PotentialInteractionPotentialInteraction(x[0], x[1]):
                    if np.count_nonzero(self.PairDistPairDist(x[0], x[1]) < self.contact_dcontact_d):
                        self._interacting_chains_interacting_chains.append(x)
        return self._interacting_chains_interacting_chains
    
    def GetChain(self, chain_name):
        """ Get chain by name
 
        :param chain_name: Chain in :attr:`~view`
        :type chain_name: :class:`str`
        """ 
        chain = self.viewview.FindChain(chain_name)
        if not chain.IsValid():
            raise RuntimeError(f"view has no chain named \"{chain_name}\"")
        return chain
 
    def GetSequence(self, chain_name):
        """ Get sequence of chain
 
        Returns sequence of specified chain as raw :class:`str`
 
        :param chain_name: Chain in :attr:`~view`
        :type chain_name: :class:`str`
        """
        if chain_name not in self._sequence_sequence:
            ch = self.GetChainGetChain(chain_name)
            s = ''.join([r.one_letter_code for r in ch.residues])
            self._sequence_sequence[chain_name] = s
        return self._sequence_sequence[chain_name]
 
    def GetPos(self, chain_name):
        """ Get representative positions of chain
 
        That's CB positions for peptide residues (CA for GLY) and C3' for
        nucleotides. Returns positions as a numpy array of shape
        (n_residues, 3).
 
        :param chain_name: Chain in :attr:`~view`
        :type chain_name: :class:`str`
        """
        if chain_name not in self._pos_pos:
            ch = self.GetChainGetChain(chain_name)
            pos = np.zeros((len(ch.residues), 3))
            for i, r in enumerate(ch.residues):
                pos[i,:] = r.atoms[0].GetPos().data
            self._pos_pos[chain_name] = pos
        return self._pos_pos[chain_name]
 
    def PairDist(self, chain_name_one, chain_name_two):
        """ Get pairwise distances between two chains
 
        Returns distances as numpy array of shape (a, b).
        Where a is the number of residues of the chain that comes BEFORE the
        other in :attr:`~chain_names` 
        """
        key = (min(chain_name_one, chain_name_two),
               max(chain_name_one, chain_name_two))
        if key not in self._pair_dist_pair_dist:
            self._pair_dist_pair_dist[key] = distance.cdist(self.GetPosGetPos(key[0]),
                                                  self.GetPosGetPos(key[1]),
                                                  'euclidean')
        return self._pair_dist_pair_dist[key]
 
    def GetMinPos(self, chain_name):
        """ Get min x,y,z cooridnates for given chain
 
        Based on positions that are extracted with GetPos
 
        :param chain_name: Chain in :attr:`~view`
        :type chain_name: :class:`str`
        """
        if chain_name not in self._min_pos_min_pos:
            self._min_pos_min_pos[chain_name] = self.GetPosGetPos(chain_name).min(0)
        return self._min_pos_min_pos[chain_name]
 
    def GetMaxPos(self, chain_name):
        """ Get max x,y,z cooridnates for given chain
 
        Based on positions that are extracted with GetPos
 
        :param chain_name: Chain in :attr:`~view`
        :type chain_name: :class:`str`
        """
        if chain_name not in self._max_pos_max_pos:
            self._max_pos_max_pos[chain_name] = self.GetPosGetPos(chain_name).max(0)
        return self._max_pos_max_pos[chain_name]
 
    def PotentialInteraction(self, chain_name_one, chain_name_two):
        """ Returns True if chains potentially interact
 
        Based on crude collision detection. There is no guarantee
        that they actually interact if True is returned. However,
        if False is returned, they don't interact for sure.
 
        :param chain_name_one: Chain in :attr:`~view`
        :type chain_name_one: class:`str`
        :param chain_name_two: Chain in :attr:`~view`
        :type chain_name_two: class:`str`
        """
        min_one = self.GetMinPosGetMinPos(chain_name_one)
        max_one = self.GetMaxPosGetMaxPos(chain_name_one)
        min_two = self.GetMinPosGetMinPos(chain_name_two)
        max_two = self.GetMaxPosGetMaxPos(chain_name_two)
        if np.max(min_one - max_two) > self.contact_dcontact_d:
            return False
        if np.max(min_two - max_one) > self.contact_dcontact_d:
            return False
        return True
 
class QSScorerResult:
    """
    Holds data relevant for QS-score computation. Formulas for QS scores:
 
    ::
 
      - QS_best = weighted_scores / (weight_sum + weight_extra_mapped)
      - QS_global = weighted_scores / (weight_sum + weight_extra_all)
      -> weighted_scores = sum(w(min(d1,d2)) * (1 - abs(d1-d2)/12)) for shared
      -> weight_sum = sum(w(min(d1,d2))) for shared
      -> weight_extra_mapped = sum(w(d)) for all mapped but non-shared
      -> weight_extra_all = sum(w(d)) for all non-shared
      -> w(d) = 1 if d <= 5, exp(-2 * ((d-5.0)/4.28)^2) else
 
    In the formulas above:
 
    * "d": CA/CB-CA/CB distance of an "inter-chain contact" ("d1", "d2" for
      "shared" contacts).
    * "mapped": we could map chains of two structures and align residues in
      :attr:`alignments`.
    * "shared": pairs of residues which are "mapped" and have
      "inter-chain contact" in both structures.
    * "inter-chain contact": CB-CB pairs (CA for GLY) with distance <= 12 A
      (fallback to CA-CA if :attr:`calpha_only` is True).
    * "w(d)": weighting function (prob. of 2 res. to interact given CB distance)
      from `Xu et al. 2009 <https://dx.doi.org/10.1016%2Fj.jmb.2008.06.002>`_.
    """
    def __init__(self, weighted_scores, weight_sum, weight_extra_mapped,
                 weight_extra_all, complete_mapping):
        self._weighted_scores_weighted_scores = weighted_scores
        self._weight_sum_weight_sum = weight_sum
        self._weight_extra_mapped_weight_extra_mapped = weight_extra_mapped
        self._weight_extra_all_weight_extra_all = weight_extra_all
        self._complete_mapping_complete_mapping = complete_mapping
 
    @property
    def weighted_scores(self):
        """ weighted_scores attribute as described in formula section above
 
        :type: :class:`float`
        """
        return self._weighted_scores_weighted_scores
 
    @property
    def weight_sum(self):
        """ weight_sum attribute as described in formula section above
 
        :type: :class:`float`
        """
        return self._weight_sum_weight_sum
 
    @property
    def weight_extra_mapped(self):
        """ weight_extra_mapped attribute as described in formula section above
 
        :type: :class:`float`
        """
        return self._weight_extra_mapped_weight_extra_mapped
 
    @property
    def weight_extra_all(self):
        """ weight_extra_all attribute as described in formula section above
 
        :type: :class:`float`
        """
        return self._weight_extra_all_weight_extra_all
 
    @property
    def complete_mapping(self):
        """ Whether the underlying mapping of the scored assemblies is complete
 
        In other words: If they have the same stoichiometry. This is relevant
        for :attr:`~QS_best` and :attr:`~QS_global` in case of no contacts in
        any of the scored entities.
 
        :type: :class:`bool`
        """
        return self._complete_mapping_complete_mapping
 
    @property
    def QS_best(self):
        """ QS_best - the actual score as described in formula section above
 
        If there are no contacts observed in any of the scored entities this
        score is 1.0 if we're comparing structures with
        :attr:`~complete_mapping`, 0.0 otherwise. In the example of two
        monomers, no contacts can be observed but they exactly match in terms
        of quaternary structure. Thus a perfect score. In terms of higher order
        structure that becomes a bit more abstract but in principle they still
        have the exact same quaternary structure if they match in stoichiometry
        but have no single contact.
 
        :type: :class:`float`
        """
        nominator = self.weighted_scoresweighted_scores
        denominator = self.weight_sumweight_sum + self.weight_extra_mappedweight_extra_mapped
        if denominator != 0.0:
            return nominator/denominator
        elif self.complete_mappingcomplete_mapping:
            return 1.0
        else:
            return 0.0
 
    @property
    def QS_global(self):
        """ QS_global - the actual score as described in formula section above
 
        If there are no contacts observed in any of the scored entities this
        score is 1.0 if we're comparing structures with
        :attr:`~complete_mapping`, 0.0 otherwise. In the example of two
        monomers, no contacts can be observed but they exactly match in terms
        of quaternary structure. Thus a perfect score. In terms of higher order
        structure that becomes a bit more abstract but in principle they still
        have the exact same quaternary structure if they match in stoichiometry
        but have no single contact.
 
        :type: :class:`float`
        """
        nominator = self.weighted_scoresweighted_scores
        denominator = self.weight_sumweight_sum + self.weight_extra_allweight_extra_all
        if denominator != 0.0:
            return nominator/denominator
        elif self.complete_mappingcomplete_mapping:
            return 1.0
        else:
            return 0.0
 
 
class QSScorer:
    """ Helper object to compute QS-score
 
    Tightly integrated into the mechanisms from the chain_mapping module.
    The prefered way to derive an object of type :class:`QSScorer` is through
    the static constructor: :func:`~FromMappingResult`. Example score
    computation including mapping:
 
    ::
 
        from ost.mol.alg.qsscore import QSScorer
        from ost.mol.alg.chain_mapping import ChainMapper
 
        ent_1 = io.LoadPDB("path_to_assembly_1.pdb")
        ent_2 = io.LoadPDB("path_to_assembly_2.pdb")
 
        chain_mapper = ChainMapper(ent_1)
        mapping_result = chain_mapper.GetlDDTMapping(ent_2)
        qs_scorer = QSScorer.FromMappingResult(mapping_result)
        score_result = qs_scorer.Score(mapping_result.mapping)
        print("score:", score_result.QS_global)
 
    QS-score computation in :func:`QSScorer.Score` implements caching.
    Repeated computations with alternative chain mappings thus become faster.
 
    :param target: Structure designated as "target". Can be fetched from
                   :class:`ost.mol.alg.chain_mapping.MappingResult`
    :type target: :class:`ost.mol.EntityView`/:class:`ost.mol.EntityHandle`
    :param chem_groups: Groups of chemically equivalent chains in *target*.
                        Can be fetched from
                        :class:`ost.mol.alg.chain_mapping.MappingResult`
    :type chem_groups: :class:`list` of :class:`list` of :class:`str`
    :param model: Structure designated as "model". Can be fetched from
                  :class:`ost.mol.alg.chain_mapping.MappingResult`
    :type model: :class:`ost.mol.EntityView`/:class:`ost.mol.EntityHandle`
    :param alns: Each alignment is accessible with ``alns[(t_chain,m_chain)]``.
                 First sequence is the sequence of the respective chain in
                 :attr:`~qsent1`, second sequence the one from :attr:`~qsent2`.
                 Can be fetched from
                 :class:`ost.mol.alg.chain_mapping.MappingResult`
    :type alns: :class:`dict` with key: :class:`tuple` of :class:`str`, value:
                :class:`ost.seq.AlignmentHandle`
    """
    def __init__(self, target, chem_groups, model, alns, contact_d = 12.0):
 
        self._qsent1_qsent1 = QSEntity(target, contact_d = contact_d)
 
        # ensure that target chain names match the ones in chem_groups
        chem_group_ch_names = list(itertools.chain.from_iterable(chem_groups))
        if self._qsent1_qsent1.chain_names != sorted(chem_group_ch_names):
            raise RuntimeError(f"Expect exact same chain names in chem_groups "
                               f"and in target (which is processed to only "
                               f"contain peptides/nucleotides). target: "
                               f"{self._qsent1.chain_names}, chem_groups: "
                               f"{chem_group_ch_names}")
 
        self._chem_groups_chem_groups = chem_groups
        self._qsent2_qsent2 = QSEntity(model, contact_d = contact_d)
        self._alns_alns = alns
 
        # cache for mapped interface scores
        # key: tuple of tuple ((qsent1_ch1, qsent1_ch2),
        #                     ((qsent2_ch1, qsent2_ch2))
        # value: tuple with four numbers referring to QS-score formalism
        #        1: weighted_scores
        #        2: weight_sum
        #        3: weight_extra_mapped
        #        4: weight_extra_all
        self._mapped_cache_mapped_cache = dict()
 
        # cache for non-mapped interfaces in qsent1
        # key: tuple (qsent1_ch1, qsent1_ch2)
        # value: contribution of that interface to weight_extra_all
        self._qsent_1_penalties_qsent_1_penalties = dict()
 
        # same for qsent2
        self._qsent_2_penalties_qsent_2_penalties = dict()
 
    @staticmethod
    def FromMappingResult(mapping_result):
        """ The preferred way to get a :class:`QSScorer`
 
        Static constructor that derives an object of type :class:`QSScorer`
        using a :class:`ost.mol.alg.chain_mapping.MappingResult`
 
        :param mapping_result: Data source
        :type mapping_result: :class:`ost.mol.alg.chain_mapping.MappingResult`
        """
        qs_scorer = QSScorer(mapping_result.target, mapping_result.chem_groups,
                             mapping_result.model, alns = mapping_result.alns)
        return qs_scorer
 
    @property
    def qsent1(self):
        """ Represents *target*
 
        :type: :class:`QSEntity`
        """
        return self._qsent1_qsent1
 
    @property
    def chem_groups(self):
        """ Groups of chemically equivalent chains in *target*
 
        Provided at object construction
 
        :type: :class:`list` of :class:`list` of :class:`str`
        """
        return self._chem_groups_chem_groups
 
    @property
    def qsent2(self):
        """ Represents *model*
 
        :type: :class:`QSEntity`
        """
        return self._qsent2_qsent2
 
    @property
    def alns(self):
        """ Alignments between chains in :attr:`~qsent1` and :attr:`~qsent2`
 
        Provided at object construction. Each alignment is accessible with
        ``alns[(t_chain,m_chain)]``. First sequence is the sequence of the
        respective chain in :attr:`~qsent1`, second sequence the one from
        :attr:`~qsent2`.
 
        :type: :class:`dict` with key: :class:`tuple` of :class:`str`, value:
               :class:`ost.seq.AlignmentHandle`
        """
        return self._alns_alns
    
    def Score(self, mapping, check=True):
        """ Computes QS-score given chain mapping
 
        Again, the preferred way is to get *mapping* is from an object
        of type :class:`ost.mol.alg.chain_mapping.MappingResult`.
 
        :param mapping: see 
                        :attr:`ost.mol.alg.chain_mapping.MappingResult.mapping`
        :type mapping: :class:`list` of :class:`list` of :class:`str`
        :param check: Perform input checks, can be disabled for speed purposes
                      if you know what you're doing.
        :type check: :class:`bool`
        :returns: Result object of type :class:`QSScorerResult`
        """
 
        if check:
            # ensure that dimensionality of mapping matches self.chem_groups
            if len(self.chem_groupschem_groups) != len(mapping):
                raise RuntimeError("Dimensions of self.chem_groups and mapping "
                                   "must match")
            for a,b in zip(self.chem_groupschem_groups, mapping):
                if len(a) != len(b):
                    raise RuntimeError("Dimensions of self.chem_groups and "
                                       "mapping must match")
            # ensure that chain names in mapping are all present in qsent2
            for name in itertools.chain.from_iterable(mapping):
                if name is not None and name not in self.qsent2qsent2.chain_names:
                    raise RuntimeError(f"Each chain in mapping must be present "
                                       f"in self.qsent2. No match for "
                                       f"\"{name}\"")
 
        flat_mapping = dict()
        for a, b in zip(self.chem_groupschem_groups, mapping):
            flat_mapping.update({x: y for x, y in zip(a, b) if y is not None})
 
        return self.FromFlatMappingFromFlatMapping(flat_mapping)
 
    def ScoreInterface(self, trg_ch1, trg_ch2, mdl_ch1, mdl_ch2):
        """ Computes QS-score only considering one interface
 
        This only works for interfaces that are computed in :func:`Score`, i.e.
        interfaces for which the alignments are set up correctly.
 
        As all specified chains must be present, the mapping is considered
        complete which affects
        :attr:`QSScorerResult.QS_global`/:attr:`QSScorerResult.QS_best` in
        edge cases of no observed contacts.
 
        :param trg_ch1: Name of first interface chain in target
        :type trg_ch1: :class:`str`
        :param trg_ch2: Name of second interface chain in target
        :type trg_ch2: :class:`str`
        :param mdl_ch1: Name of first interface chain in model
        :type mdl_ch1: :class:`str`
        :param mdl_ch2: Name of second interface chain in model
        :type mdl_ch2: :class:`str`
        :returns: Result object of type :class:`QSScorerResult`
        :raises: :class:`RuntimeError` if no aln for trg_ch1/mdl_ch1 or
                 trg_ch2/mdl_ch2 is available.
        """
        if (trg_ch1, mdl_ch1) not in self.alnsalns:
            raise RuntimeError(f"No aln between trg_ch1 ({trg_ch1}) and "
                               f"mdl_ch1 ({mdl_ch1}) available. Did you "
                               f"construct the QSScorer object from a "
                               f"MappingResult and are trg_ch1 and mdl_ch1 "
                               f"mapped to each other?")
        if (trg_ch2, mdl_ch2) not in self.alnsalns:
            raise RuntimeError(f"No aln between trg_ch1 ({trg_ch1}) and "
                               f"mdl_ch1 ({mdl_ch1}) available. Did you "
                               f"construct the QSScorer object from a "
                               f"MappingResult and are trg_ch1 and mdl_ch1 "
                               f"mapped to each other?")
        trg_int = (trg_ch1, trg_ch2)
        mdl_int = (mdl_ch1, mdl_ch2)
        a, b, c, d = self._MappedInterfaceScores_MappedInterfaceScores(trg_int, mdl_int)
 
        # complete_mapping is True by definition, as the requested chain pairs
        # are both present
        return QSScorerResult(a, b, c, d, True)
 
    def FromFlatMapping(self, flat_mapping):
        """ Same as :func:`Score` but with flat mapping
 
        :param flat_mapping: Dictionary with target chain names as keys and
                             the mapped model chain names as value
        :type flat_mapping: :class:`dict` with :class:`str` as key and value
        :returns: Result object of type :class:`QSScorerResult`
        """
 
        weighted_scores = 0.0
        weight_sum = 0.0
        weight_extra_mapped = 0.0
        weight_extra_all = 0.0
 
        # keep track of processed interfaces in qsent2
        processed_qsent2_interfaces = set()
 
        for int1 in self.qsent1qsent1.interacting_chains:
            if int1[0] in flat_mapping and int1[1] in flat_mapping:
                int2 = (flat_mapping[int1[0]], flat_mapping[int1[1]])
                a, b, c, d = self._MappedInterfaceScores_MappedInterfaceScores(int1, int2)
                weighted_scores += a
                weight_sum += b
                weight_extra_mapped += c
                weight_extra_all += d
                processed_qsent2_interfaces.add((min(int2[0], int2[1]),
                                                 max(int2[0], int2[1])))
            else:
                weight_extra_all += self._InterfacePenalty1_InterfacePenalty1(int1)
 
        # process interfaces that only exist in qsent2
        r_flat_mapping = {v:k for k,v in flat_mapping.items()} # reverse mapping...
        for int2 in self.qsent2qsent2.interacting_chains:
            if int2 not in processed_qsent2_interfaces:
                if int2[0] in r_flat_mapping and int2[1] in r_flat_mapping:
                    int1 = (r_flat_mapping[int2[0]], r_flat_mapping[int2[1]])
                    a, b, c, d = self._MappedInterfaceScores_MappedInterfaceScores(int1, int2)
                    weighted_scores += a
                    weight_sum += b
                    weight_extra_mapped += c
                    weight_extra_all += d
                else:
                    weight_extra_all += self._InterfacePenalty2_InterfacePenalty2(int2)
 
        trg_chains = sorted(self.qsent1qsent1.chain_names) # should be sorted already
        mdl_chains = sorted(self.qsent2qsent2.chain_names) # should be sorted already
        mapped_trg_chains = sorted(flat_mapping.keys())
        mapped_mdl_chains = sorted(flat_mapping.values())
        trg_complete = trg_chains == mapped_trg_chains
        mdl_complete = mdl_chains == mapped_mdl_chains
        complete_mapping = trg_complete and mdl_complete
 
        return QSScorerResult(weighted_scores, weight_sum, weight_extra_mapped,
                              weight_extra_all, complete_mapping)
 
    def _MappedInterfaceScores(self, int1, int2):
        key_one = (int1, int2)
        if key_one in self._mapped_cache_mapped_cache:
            return self._mapped_cache_mapped_cache[key_one]
        key_two = ((int1[1], int1[0]), (int2[1], int2[0]))
        if key_two in self._mapped_cache_mapped_cache:
            return self._mapped_cache_mapped_cache[key_two]
 
        weighted_scores, weight_sum, weight_extra_mapped, weight_extra_all = \
        self._InterfaceScores_InterfaceScores(int1, int2)
        self._mapped_cache_mapped_cache[key_one] = (weighted_scores, weight_sum, weight_extra_mapped,
                                       weight_extra_all)
        return (weighted_scores, weight_sum, weight_extra_mapped, weight_extra_all)
 
    def _InterfaceScores(self, int1, int2):
 
        d1 = self.qsent1qsent1.PairDist(int1[0], int1[1])
        d2 = self.qsent2qsent2.PairDist(int2[0], int2[1])
 
        # given two chain names a and b: if a < b, shape of pairwise distances is
        # (len(a), len(b)). However, if b > a, its (len(b), len(a)) => transpose
        if int1[0] > int1[1]:
            d1 = d1.transpose()
        if int2[0] > int2[1]:
            d2 = d2.transpose()
 
        # indices of the first chain in the two interfaces
        mapped_indices_1_1, mapped_indices_1_2 = \
        self._IndexMapping_IndexMapping(int1[0], int2[0])
        # indices of the second chain in the two interfaces
        mapped_indices_2_1, mapped_indices_2_2 = \
        self._IndexMapping_IndexMapping(int1[1], int2[1])
 
        # get shared_masks - for this we first need to select the actual
        # mapped positions to get a one-to-one relationship and map it back
        # to the original mask size
        assert(self.qsent1qsent1.contact_d == self.qsent2qsent2.contact_d)
        contact_d = self.qsent1qsent1.contact_d
        mapped_idx_grid_1 = np.ix_(mapped_indices_1_1, mapped_indices_2_1)
        mapped_idx_grid_2 = np.ix_(mapped_indices_1_2, mapped_indices_2_2)
 
        if mapped_indices_1_1.shape[0] == 0 or mapped_indices_2_1.shape[0] == 0:
            # dealing with special cases where we have no mapped residues
            # we only avoid errors here when using maped_idx_grid_x for indexing
            # but run the rest of the algorithm anyways which produces some
            # computational overhead. Thats OK, as this should occur rarely
            shared_mask_d1 = np.full(d1.shape, False, dtype=bool)
            shared_mask_d2 = np.full(d2.shape, False, dtype=bool)
            mapped_nonshared_mask_d1 = np.full(d1.shape, False, dtype=bool)
            mapped_nonshared_mask_d2 = np.full(d2.shape, False, dtype=bool)
            if mapped_indices_1_1.shape[0] == 0 or \
               mapped_indices_2_1.shape[0] == 0:
                # mapped_idx_grid_1 has not a single mapped residue which raises
                # an error when calling something like d1[mapped_idx_grid_1]
                mapped_d1_contacts = np.full(d1.shape, False, dtype=bool)
            else:
                mapped_d1_contacts = d1[mapped_idx_grid_1] < contact_d
                mapped_nonshared_mask_d1[mapped_idx_grid_1] = mapped_d1_contacts
 
            if mapped_indices_1_2.shape[0] == 0 or \
               mapped_indices_2_2.shape[0] == 0:
                # mapped_idx_grid_2 has not a single mapped residue which raises
                # an error when calling something like d2[mapped_idx_grid_2]
                mapped_d2_contacts = np.full(d2.shape, False, dtype=bool)
            else:
                mapped_d2_contacts = d2[mapped_idx_grid_2] < contact_d
                mapped_nonshared_mask_d2[mapped_idx_grid_2] = mapped_d2_contacts
            shared_mask = np.full(mapped_d1_contacts.shape, False, dtype=bool)
        else:
            mapped_d1_contacts = d1[mapped_idx_grid_1] < contact_d
            mapped_d2_contacts = d2[mapped_idx_grid_2] < contact_d
            shared_mask = np.logical_and(mapped_d1_contacts, mapped_d2_contacts)
            shared_mask_d1 = np.full(d1.shape, False, dtype=bool)
            shared_mask_d1[mapped_idx_grid_1] = shared_mask
            shared_mask_d2 = np.full(d2.shape, False, dtype=bool)
            shared_mask_d2[mapped_idx_grid_2] = shared_mask
 
            # get mapped but nonshared masks
            mapped_nonshared_mask_d1 = np.full(d1.shape, False, dtype=bool)
            mapped_nonshared_mask_d1[mapped_idx_grid_1] = \
            np.logical_and(np.logical_not(shared_mask), mapped_d1_contacts)
            mapped_nonshared_mask_d2 = np.full(d2.shape, False, dtype=bool)
            mapped_nonshared_mask_d2[mapped_idx_grid_2] = \
            np.logical_and(np.logical_not(shared_mask), mapped_d2_contacts)
 
        # contributions from shared contacts
        shared_d1 = d1[shared_mask_d1]
        shared_d2 = d2[shared_mask_d2]
        shared_min = np.minimum(shared_d1, shared_d2)
        shared_abs_diff_div_12 = np.abs(np.subtract(shared_d1, shared_d2))/12.0
        weight_term = np.ones(shared_min.shape[0])
        bigger_5_mask = shared_min > 5.0
        weights = np.exp(-2.0*np.square((shared_min[bigger_5_mask]-5.0)/4.28))
        weight_term[bigger_5_mask] = weights
        diff_term = np.subtract(np.ones(weight_term.shape[0]),
                                shared_abs_diff_div_12)
        weighted_scores = np.sum(np.multiply(weight_term, diff_term))
        weight_sum = np.sum(weight_term)
 
        # do weight_extra_all for interface one
        nonshared_contact_mask_d1 = np.logical_and(np.logical_not(shared_mask_d1),
                                                   d1 < contact_d)
        contact_distances = d1[nonshared_contact_mask_d1]
        bigger_5 = contact_distances[contact_distances > 5]
        weight_extra_all = np.sum(np.exp(-2.0*np.square((bigger_5-5.0)/4.28)))
        # add 1.0 for all contact distances <= 5.0
        weight_extra_all += contact_distances.shape[0] - bigger_5.shape[0]
        # same for interface two
        nonshared_contact_mask_d2 = np.logical_and(np.logical_not(shared_mask_d2),
                                                   d2 < contact_d)
        contact_distances = d2[nonshared_contact_mask_d2]
        bigger_5 = contact_distances[contact_distances > 5]
        weight_extra_all += np.sum(np.exp(-2.0*np.square((bigger_5-5.0)/4.28)))
        # add 1.0 for all contact distances <= 5.0
        weight_extra_all += contact_distances.shape[0] - bigger_5.shape[0]
 
        # do weight_extra_mapped for interface one
        contact_distances = d1[mapped_nonshared_mask_d1]
        bigger_5 = contact_distances[contact_distances > 5]
        weight_extra_mapped = np.sum(np.exp(-2.0*np.square((bigger_5-5.0)/4.28)))
        # add 1.0 for all contact distances <= 5.0
        weight_extra_mapped += contact_distances.shape[0] - bigger_5.shape[0]
        # same for interface two
        contact_distances = d2[mapped_nonshared_mask_d2]
        bigger_5 = contact_distances[contact_distances > 5]
        weight_extra_mapped += np.sum(np.exp(-2.0*np.square((bigger_5-5.0)/4.28)))
        # add 1.0 for all contact distances <= 5.0
        weight_extra_mapped += contact_distances.shape[0] - bigger_5.shape[0]
 
        return (weighted_scores, weight_sum, weight_extra_mapped, weight_extra_all)
 
    def _IndexMapping(self, ch1, ch2):
        """ Fetches aln and returns indices of (non-)aligned residues
 
        returns 2 numpy arrays containing the indices of residues in
        ch1 and ch2 which are aligned
        """
        mapped_indices_1 = list()
        mapped_indices_2 = list()
        idx_1 = 0
        idx_2 = 0
        for col in self.alnsalns[(ch1, ch2)]:
            if col[0] != '-' and col[1] != '-':
                mapped_indices_1.append(idx_1)
                mapped_indices_2.append(idx_2)
            if col[0] != '-':
                idx_1 +=1
            if col[1] != '-':
                idx_2 +=1
        return (np.array(mapped_indices_1), np.array(mapped_indices_2))
 
    def _InterfacePenalty1(self, interface):
        if interface not in self._qsent_1_penalties_qsent_1_penalties:
            self._qsent_1_penalties_qsent_1_penalties[interface] = \
            self._InterfacePenalty_InterfacePenalty(self.qsent1qsent1, interface)
        return self._qsent_1_penalties_qsent_1_penalties[interface]
 
    def _InterfacePenalty2(self, interface):
        if interface not in self._qsent_2_penalties_qsent_2_penalties:
            self._qsent_2_penalties_qsent_2_penalties[interface] = \
            self._InterfacePenalty_InterfacePenalty(self.qsent2qsent2, interface)
        return self._qsent_2_penalties_qsent_2_penalties[interface]
 
    def _InterfacePenalty(self, qsent, interface):
        d = qsent.PairDist(interface[0], interface[1])
        contact_distances = d[d < qsent.contact_d]
        bigger_5 = contact_distances[contact_distances > 5]
        penalty = np.sum(np.exp(-2.0*np.square((bigger_5-5.0)/4.28)))
        # add 1.0 for all contact distances <= 5.0
        penalty += contact_distances.shape[0] - bigger_5.shape[0]
        return penalty
 
# specify public interface
__all__ = ('QSEntity', 'QSScorer', 'QSScorerResult')