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haddock3 / data /src /haddock /libs /libscan.py
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"""Shared helpers for the mutagenesis scan modules.
The ``alascan`` (alanine), ``rnascan`` (RNA base) and ``dnascan`` (DNA base
pair) analysis modules share the same scoring, z-score, cluster-output,
b-factor and TSV-writing machinery. The common, module-agnostic pieces live
here; each module keeps only its own mutation logic (which residues/atoms are
mutated, how the interface is scanned, and how mutation jobs are executed).
"""

import io
import os
import shutil
from contextlib import redirect_stdout
from dataclasses import dataclass
from pathlib import Path
from typing import Any, Dict, List, Optional, Tuple, Union

import numpy as np
import pandas as pd

from haddock import log
from haddock.clis import cli_score
from haddock.core.exceptions import ConfigurationError
from haddock.libs.libontology import PDBFile
from haddock.libs.libplots import make_alascan_plot, make_rnascan_plot


# ---------------------------------------------------------------------------
# Nucleic-acid mutation helpers (shared by the rnascan and dnascan modules)
# ---------------------------------------------------------------------------
# The two nucleic-acid scan modules mutate bases the same way; only the residue
# naming (one-letter RNA vs two-letter DNA) and the backbone atom set (RNA keeps
# the 2'-hydroxyl O2') differ. The chemistry-invariant pieces live here so both
# modules share a single implementation.

# Base ring atoms shared by both purines. Preserving them when mutating one
# purine into the other keeps the base plane and glycosidic orientation, so CNS
# only has to rebuild the differing substituents.
PURINE_BASE_ATOMS = ["N9", "C8", "N7", "C5", "C4", "N3", "C2", "N1", "C6"]

# Base ring atoms shared by both pyrimidines. Same rationale as for the purines.
PYRIMIDINE_BASE_ATOMS = ["N1", "C2", "O2", "N3", "C4", "C5", "C6"]

# Glycosidic-region anchor atoms kept (and renamed) on cross-type mutations
# (purine <-> pyrimidine). Because the purine and pyrimidine ring systems do not
# share atom names, these three atoms are preserved and renamed to their
# counterpart in the target ring so that CNS rebuilds the new base with the
# correct glycosidic orientation. The correspondence is:
#   pyrimidine N1 <-> purine N9   (glycosidic nitrogen)
#   pyrimidine C2 <-> purine C4
#   pyrimidine C6 <-> purine C8
_PYRIMIDINE_TO_PURINE_ANCHORS = {"N1": "N9", "C2": "C4", "C6": "C8"}
_PURINE_TO_PYRIMIDINE_ANCHORS = {"N9": "N1", "C4": "C2", "C8": "C6"}


def norm_atom_name(atom_name: str) -> str:
    """Normalise atom names so that primes are always written as `'`."""
    return atom_name.replace("*", "'")


def get_atoms_to_keep(
    ori_resname: str,
    target_resname: str,
    *,
    backbone_atoms: List[str],
    purines: Tuple[str, ...],
    pyrimidines: Tuple[str, ...],
) -> Dict[str, str]:
    """Return the atoms to preserve when mutating one nucleic-acid base into
    another.
    The result maps each atom name to keep (as found in the original residue) to
    the atom name it must be written with in the mutated residue. Backbone atoms
    and same-ring-type base atoms keep their name (mapped to themselves).
    The sugar-phosphate backbone (``backbone_atoms``) is always kept. When the
    original and target bases are of the same ring type (both purines or both
    pyrimidines) the base ring atoms common to that type are kept as well, so
    that the base orientation is preserved and CNS only rebuilds the differing
    substituents. For cross-type mutations (purine <-> pyrimidine) the three
    glycosidic-region anchor atoms are kept and renamed to their counterpart in
    the target ring system.
    Parameters
    ----------
    ori_resname : str
        Original (wild-type) residue name.
    target_resname : str
        Target base residue name.
    backbone_atoms : list of str
        Sugar-phosphate backbone atoms to always keep (RNA keeps ``O2'``, DNA
        does not).
    purines, pyrimidines : tuple of str
        Residue names classified as purines / pyrimidines for this module.
    Returns
    -------
    dict of str -> str
        Mapping of original atom name -> atom name to write for the mutated
        nucleotide.
    """
    # Backbone is always kept, with unchanged atom names.
    atoms_to_keep: Dict[str, str] = {atom: atom for atom in backbone_atoms}
    if ori_resname in purines and target_resname in purines:
        atoms_to_keep.update({atom: atom for atom in PURINE_BASE_ATOMS})
    elif ori_resname in pyrimidines and target_resname in pyrimidines:
        atoms_to_keep.update({atom: atom for atom in PYRIMIDINE_BASE_ATOMS})
    elif ori_resname in pyrimidines and target_resname in purines:
        atoms_to_keep.update(_PYRIMIDINE_TO_PURINE_ANCHORS)
    elif ori_resname in purines and target_resname in pyrimidines:
        atoms_to_keep.update(_PURINE_TO_PYRIMIDINE_ANCHORS)
    return atoms_to_keep


def validate_scan_bases(
    scan_bases: List[str],
    allowed: Tuple[str, ...],
    *,
    base_kind: str,
    allowed_note: str,
) -> List[str]:
    """Validate and normalise a list of target nucleic-acid bases.
    Entries are upper-cased and de-duplicated (keeping first-seen order) and
    must belong to ``allowed``.
    Parameters
    ----------
    scan_bases : list of str
        Target bases requested by the user.
    allowed : tuple of str
        Canonical residue names accepted by the calling module.
    base_kind : str
        Human-readable base family (e.g. ``"RNA"`` or ``"DNA"``) used in the
        "empty list" error message.
    allowed_note : str
        Sentence describing the accepted values (and why the other naming is
        rejected) used in the "invalid entry" error message.
    Returns
    -------
    list of str
        Normalised, de-duplicated list of canonical residue names, in the order
        first seen.
    Raises
    ------
    ConfigurationError
        If ``scan_bases`` is empty or contains an unrecognised base.
    """
    if not scan_bases:
        raise ConfigurationError(
            f"'scan_bases' must contain at least one {base_kind} base "
            f"among {', '.join(allowed)}."
        )
    normalised: List[str] = []
    for base in scan_bases:
        canonical = str(base).strip().upper()
        if canonical not in allowed:
            raise ConfigurationError(
                f"Invalid 'scan_bases' entry {base!r}. Allowed values are the "
                f"{allowed_note}"
            )
        if canonical not in normalised:
            normalised.append(canonical)
    return normalised


def filter_interface(
    interface: Dict[str, List[int]],
    filter_resdic: Dict[str, List[int]],
    user_chains: List[str],
) -> Dict[str, List[int]]:
    """Restrict the detected interface to the user-selected residues/chains.
    If the user provided target residues (``resdic_*``), the interface is
    intersected with them. Otherwise, if the user provided target chains, the
    interface is restricted to those chains. With neither, the interface is
    returned unchanged.
    Parameters
    ----------
    interface : dict
        Mapping of chain id to its list of interface residue numbers.
    filter_resdic : dict
        Mapping of chain id to user-requested residue numbers. The sentinel
        ``{"_": []}`` means "no residue restriction".
    user_chains : list of str
        User-requested chain ids (used only when no residue restriction is set).
    Returns
    -------
    dict
        The filtered interface.
    """
    # if user defined target residues, check they are in the interface
    if filter_resdic != {"_": []}:
        filtered_interface = {}
        for chain in filter_resdic:
            if chain in interface:
                # intersection of user queried residues and interface residues
                user_res_valid = list(
                    set(filter_resdic[chain]).intersection(set(interface[chain]))
                )
                # keep the chain only if at least one residue survives
                if user_res_valid:
                    filtered_interface[chain] = user_res_valid
        return filtered_interface
    # if (user defined target chains) & (no user target residues) - use them
    if user_chains:
        return {chain: res for chain, res in interface.items() if chain in user_chains}
    return interface


def build_resname_dict(coords: Dict[Tuple, object]) -> Dict[str, str]:
    """Map ``"{chain}-{resid}"`` to its residue name from a coordinate dict.
    Parameters
    ----------
    coords : dict
        Coordinate dictionary keyed by ``(chain, resid, atom_name, resname)``
        tuples, as returned by ``load_coords(..., add_resname=True)``.
    Returns
    -------
    dict
        Mapping of ``"{chain}-{resid}"`` to the residue name (first occurrence).
    """
    resname_dict: Dict[str, str] = {}
    for chain, resid, _atom, resname in coords.keys():
        key = f"{chain}-{resid}"
        if key not in resname_dict:
            resname_dict[key] = resname
    return resname_dict


def make_scan_plot(
    df: pd.DataFrame,
    clt_id,
    scan_res: str = "residue",
    offline: bool = False,
    splitplot: bool = False,
    xaxis_title: str = "Residue Name",
) -> str:
    """Generate a scan cluster plot (harmonised across scan modules).
    Shared plotting entry point for the ``alascan``, ``rnascan`` and ``dnascan``
    modules. Depending on ``splitplot`` the energy components are either drawn
    as separate stacked panels (one panel per energy term) or overlaid in a
    single grouped-bar panel.
    Parameters
    ----------
    df : pandas.DataFrame
        Cluster scan data to plot.
    clt_id : int or str
        Cluster identifier.
    scan_res : str, optional
        Label used for the scan (e.g. ``"ALA"``, ``"RNA base"``).
    offline : bool, optional
        Whether the plot must be functional offline, by default False.
    splitplot : bool, optional
        If True draw one panel per energy component; if False (default) overlay
        all components in a single panel.
    xaxis_title : str, optional
        Label of the x-axis, by default "Residue Name". Mutational scans use
        "Mutation" instead.
    Returns
    -------
    html_output_filename : str
        Name of the plot generated.
    """
    plot_func = make_rnascan_plot if splitplot else make_alascan_plot
    return plot_func(
        df,
        clt_id,
        scan_res=scan_res,
        offline=offline,
        xaxis_title=xaxis_title,
    )


@dataclass
class MutationResult:
    """Result from a single mutation.
    The ``partner_*`` fields are only used by modules that perform paired
    (double) mutations, such as ``dnascan`` (base-pair mutations); they default
    to ``None`` for single-residue mutations (``alascan``, ``rnascan``).
    """

    model_id: str
    chain: str
    resid: int
    ori_resname: str
    target_resname: str
    # components of "mutant_scores": score, vdw, elec, desolv, bsa
    mutant_scores: Tuple[float, float, float, float, float]
    delta_scores: Tuple[float, float, float, float, float]
    success: bool
    error_msg: Optional[str] = None
    partner_chain: Optional[str] = None
    partner_resid: Optional[int] = None
    partner_ori_resname: Optional[str] = None
    partner_target_resname: Optional[str] = None


def get_score_string(
    pdb_f: str,
    run_dir: str,
    outputpdb: bool = False,
    ligand_param_fname: Union[Path, str] = "",
    ligand_top_fname: Union[Path, str] = "",
) -> List[str]:
    """Get score output from cli_score.main.
    Parameters
    ----------
    pdb_f : str
        Path to the pdb file.
    run_dir : str
        Path to the run directory.
    outputpdb : bool, optional
        If True, the output, energy-minimized pdb file will be written.
        Default is False.
    ligand_param_fname : Union[Path, str]
        Path to additional parameter file used by CNS.
    ligand_top_fname : Union[Path, str]
        Path to additional topology file used by CNS.
    Returns
    -------
    out : list[str]
        List of strings with the score output.
    """
    stdout = io.StringIO()
    with redirect_stdout(stdout):
        cli_score.main(
            pdb_f,
            run_dir,
            full=True,
            outputpdb=outputpdb,
            ligand_param_fname=ligand_param_fname,
            ligand_top_fname=ligand_top_fname,
        )
    out = stdout.getvalue().split(os.linesep)
    return out


def calc_score(
    pdb_f: str,
    run_dir: str,
    outputpdb: bool = False,
    ligand_param_fname: Union[Path, str] = "",
    ligand_top_fname: Union[Path, str] = "",
) -> Tuple[float, float, float, float, float]:
    """Calculate the score of a model.
    Parameters
    ----------
    pdb_f : str
        Path to the pdb file.
    run_dir : str
        Path to the run directory.
    outputpdb : bool, optional
        If True, the output, energy-minimized pdb file will be written.
        Default is False.
    ligand_param_fname : Union[Path, str]
        Path to additional parameter file used by CNS
    ligand_top_fname : Union[Path, str]
        Path to additional topology file used by CNS
    Returns
    -------
    Tuple[float, float, float, float, float]
        All the scores
    score : float
        Haddock score.
    vdw : float
        Van der Waals energy.
    elec : float
        Electrostatic energy.
    desolv : float
        Desolvation energy.
    bsa : float
        Buried surface area.
    Raises
    ------
    FileNotFoundError
        Error when the file could not be located.
    """
    scores_strings = get_score_string(
        pdb_f,
        run_dir,
        outputpdb=outputpdb,
        ligand_param_fname=ligand_param_fname,
        ligand_top_fname=ligand_top_fname,
    )
    # Loop over lines to search for the score and components
    for ln in scores_strings:
        if ln.startswith("> HADDOCK-score (emscoring)"):
            score = float(ln.split()[-1])
        if ln.startswith("> vdw"):
            vdw = float(ln.split("vdw=")[1].split(",")[0])
            elec = float(ln.split("elec=")[1].split(",")[0])
            desolv = float(ln.split("desolv=")[1].split(",")[0])
            bsa = float(ln.split("bsa=")[1].split(",")[0])
        if ln.startswith("> writing") and outputpdb:
            outpdb = ln.split()[-1]
            # check if the output pdb file exists
            if not os.path.exists(outpdb):
                raise FileNotFoundError(f"Could not find output pdb file {outpdb}")
    return score, vdw, elec, desolv, bsa


def add_zscores(df_scan_clt, column="delta_score"):
    """Add z-scores to the dataframe.
    Parameters
    ----------
    df_scan : pandas.DataFrame
        Dataframe with the scan results for the model.
    colunm : str
        Column to calculate the z-score.
    Returns
    -------
    df_scan : pandas.DataFrame
        Dataframe with the z-scores added.
    """
    mean_delta = np.mean(df_scan_clt[column])
    std_delta = np.std(df_scan_clt[column])
    if std_delta > 0.0:
        df_scan_clt["z_score"] = (df_scan_clt[column] - mean_delta) / std_delta
    else:
        df_scan_clt["z_score"] = 0.0
    return df_scan_clt


class AddDeltaBFactor:
    """Add the (normalised) delta score into the b-factor column of a PDB.
    Subclasses set :attr:`module_name` (used for the output filename suffix,
    ``<model>_<module_name>.pdb``) and may override :meth:`_residue_keys` to
    control which residues each mutation result is attributed to (e.g. both
    nucleotides of a base pair for ``dnascan``).
    """

    #: filename suffix / module identifier; overridden by subclasses
    module_name: str = "scan"

    def __init__(
        self,
        model: PDBFile,
        path: Path,
        model_results: List[MutationResult],
    ):
        """Initialisation function
        Parameters
        ----------
        model : PDBFile
            PDBfile model to be modified
        path : Path
            Where to write the new file
        """
        self.model = model
        self.path = path
        self.input_results = model_results

    def run(self) -> PDBFile:
        """Perform the addition of delta scores as bfactor in pdb file."""
        self.reorder_results()
        # Define new pdb filename
        model_fname = self.model.file_name.removesuffix(".pdb")
        output_fname = f"{model_fname}_{self.module_name}.pdb"
        # Add delta_score as a bfactor to the model
        self.write_delta_score_to_pdb(output_fname)
        # Update attributes of the model
        self.model.ori_name = self.model.file_name
        self.model.file_name = output_fname
        self.model.full_name = output_fname
        self.model.rel_path = Path("..", Path(self.path).name, output_fname)
        self.model.path = str(Path(".").resolve())
        return self.model

    def _residue_keys(self, mut_result: MutationResult) -> List[Tuple[str, int]]:
        """Return the ``(chain, resid)`` keys a mutation result applies to.
        By default a result applies only to its own residue. Modules that
        perform paired mutations override this to also colour the partner.
        """
        return [(mut_result.chain, mut_result.resid)]

    def reorder_results(self) -> None:
        """Aggregate mutation results into a per-residue delta score map.
        Organise mutation results into a dictionary with ``chain-resid`` keys
        and, as values, the mean delta score over all mutations attributed to
        that residue (e.g. ``{"A-115": 5.2}``), and determine the min and max
        score within the model to normalise the data.
        """
        # First gather every delta score observed for each residue
        per_residue_scores: Dict[str, List[float]] = {}
        for mut_result in self.input_results:
            for chain, resid in self._residue_keys(mut_result):
                chain_res_key = f"{chain}-{resid}"
                per_residue_scores.setdefault(chain_res_key, []).append(
                    mut_result.delta_scores[0]
                )
        # Average the delta scores attributed to each residue
        self.model_results: Dict[str, float] = {}
        all_delta_scores: List[float] = []
        for chain_res_key, delta_scores in per_residue_scores.items():
            mean_delta = float(np.mean(delta_scores))
            self.model_results[chain_res_key] = mean_delta
            all_delta_scores.append(mean_delta)
        # Obtain min and max delta score to be able to normalize later
        if len(all_delta_scores) >= 1:
            self.min_score = min(all_delta_scores)
            self.max_score = max(all_delta_scores)
        else:
            self.min_score = -1
            self.max_score = 1

    def write_delta_score_to_pdb(self, output_path: Path) -> Path:
        """Add delta scores as b-factors in PDB file.
        Parameters
        ----------
        output_path : Path
            Path to the pdb file.
        Returns
        -------
        output_path : Path
            Path to the pdb file with the b-factors added.
        """
        # Input pdb file path
        input_pdbfile = Path(self.model.path, self.model.file_name)
        # Start writting file containing bfactor
        with open(input_pdbfile, "r") as fin, open(output_path, "w") as fout:
            for line in fin:
                if line.startswith("ATOM"):
                    chain = line[21]
                    resid = int(line[22:26])
                    chain_res_key = f"{chain}-{resid}"
                    try:
                        delta_score = self.model_results[chain_res_key]
                        norm_delta = self.normalize_score(delta_score)
                    except KeyError:
                        norm_delta = 0.0
                    # Generate the bfactor string
                    delta_str = f"{norm_delta:.2f}".rjust(6, " ")
                    # Modify the PDB line
                    line = line[:60] + delta_str + line[66:]
                fout.write(line)
        return output_path

    def normalize_score(self, score: float) -> float:
        """Normalise the input score based on observed scores for this model
        In case normalisation cannot be performed, returns 50.0
        Parameters
        ----------
        score : float
            Input score to be normalized
        Returns
        -------
        norm100 : float
            Normalized score between 0 and 100
        """
        try:
            norm = (score - self.min_score) / (self.max_score - self.min_score)
        except ZeroDivisionError:
            norm = 0.5
        norm100 = 100 * norm
        return norm100


#: statistics columns appended after the per-module identity columns in the
#: cluster TSV output (mean/std of each energy term plus the population fraction)
CLUSTER_STAT_COLUMNS = [
    "delta_score",
    "delta_score_std",
    "delta_vdw",
    "delta_vdw_std",
    "delta_elec",
    "delta_elec_std",
    "delta_desolv",
    "delta_desolv_std",
    "delta_bsa",
    "delta_bsa_std",
    "frac_pres",
]


class ClusterOutputer:
    """Base class writing the per-cluster scan TSV (and optional plot).
    Subclasses provide the module-specific identity columns/rows (which depend
    on whether a mutation is a single residue or a base pair) via
    :meth:`_identity_columns` and :meth:`_identity_row`, and set the class
    attributes :attr:`module_name`, :attr:`sort_columns`,
    :attr:`zscore_reference` and :attr:`default_scan_residue`. The averaging,
    z-scoring, sorting, file writing and (harmonised) plot handling are shared.
    """

    module_name: str = "scan"
    default_scan_residue: str = "residue"
    sort_columns = ["chain", "resid"]
    zscore_reference: str = "residues"
    #: x-axis label of the cluster plot; mutational scans override it
    plot_xaxis_title: str = "Residue Name"

    def __init__(
        self,
        cluster_scan_data: Dict[str, Dict[str, Union[float, int]]],
        clt_id: str,
        clt_population: int,
        scan_residue: Optional[str] = None,
        generate_plot: bool = False,
        offline: bool = False,
        splitplot: bool = False,
    ):
        """Initialization function
        Parameters
        ----------
        cluster_scan_data : Dict[str, Dict[str, Union[float, int]]]
            Dictionary containing scan data per mutation identifier.
        clt_id : str
            Cluster identifier
        clt_population : int
            Number of entries in this cluster.
        scan_residue : str, optional
            Label of the scan; defaults to the class' ``default_scan_residue``.
        generate_plot : bool, optional
            Defines if a plot must be generated, by default False
        offline : bool, optional
            Defines if the plot should be functional offline, by default False
        splitplot : bool, optional
            If True draw one plot panel per energy component; if False (default)
            overlay all components in a single panel.
        """
        self.cluster_scan_data = cluster_scan_data
        self.clt_id = clt_id
        self.clt_population = clt_population
        self.scanned_residue = (
            scan_residue if scan_residue is not None else self.default_scan_residue
        )
        self.generate_plot = generate_plot
        self.offline = offline
        self.splitplot = splitplot

    def _identity_columns(self) -> List[str]:
        """Return the identity column names preceding the statistics columns."""
        raise NotImplementedError

    def _identity_row(self, ident, clt_res_dt) -> list:
        """Return the identity values for one mutation identifier."""
        raise NotImplementedError

    def _extra_header_lines(self) -> List[str]:
        """Return extra comment lines to add to the TSV header (no leading #)."""
        return []

    def _stat_values(self, clt_res_dt) -> list:
        """Return the averaged statistics values for one mutation identifier."""
        return [
            np.mean(clt_res_dt["delta_score"]),
            np.std(clt_res_dt["delta_score"]),
            np.mean(clt_res_dt["delta_vdw"]),
            np.std(clt_res_dt["delta_vdw"]),
            np.mean(clt_res_dt["delta_elec"]),
            np.std(clt_res_dt["delta_elec"]),
            np.mean(clt_res_dt["delta_desolv"]),
            np.std(clt_res_dt["delta_desolv"]),
            np.mean(clt_res_dt["delta_bsa"]),
            np.std(clt_res_dt["delta_bsa"]),
            clt_res_dt["frac_pr"] / self.clt_population,
        ]

    def run(self) -> str:
        """Write cluster scan output to a scan_clt_X.tsv file (and plot).
        Return
        ------
        scan_clt_filename : str
            Name of the tsv file written
        """
        clt_data = []
        for ident, clt_res_dt in self.cluster_scan_data.items():
            clt_data.append(
                self._identity_row(ident, clt_res_dt) + self._stat_values(clt_res_dt)
            )
        df_cols = self._identity_columns() + CLUSTER_STAT_COLUMNS
        df_scan_clt = pd.DataFrame(clt_data, columns=df_cols)
        # adding clt-based Z score
        df_scan_clt = add_zscores(df_scan_clt, "delta_score")
        # Sort rows
        df_scan_clt.sort_values(by=self.sort_columns, inplace=True)
        # Generate output CSV data
        csv_data = io.StringIO()
        df_scan_clt.to_csv(csv_data, index=False, float_format="%.2f", sep="\t")
        csv_data.seek(0)
        # Define output csv filepath
        scan_clt_filename = f"scan_clt_{self.clt_id}.tsv"
        # Write the file
        with open(scan_clt_filename, "w") as fout:
            fout.write(f"{'#' * 80}{os.linesep}")
            fout.write(
                f"# `{self.module_name}` cluster results for cluster "
                f"{self.clt_id}{os.linesep}"
            )
            fout.write(f"# reported values are the average for the cluster{os.linesep}")
            fout.write(f"#{os.linesep}")
            for extra in self._extra_header_lines():
                fout.write(f"# {extra}{os.linesep}")
            fout.write(
                f"# z_score is calculated with respect to the mean values of all "
                f"{self.zscore_reference}{os.linesep}"
            )
            fout.write(f"{'#' * 80}{os.linesep}")
            fout.write(csv_data.read())

        # Generate plot
        self.gen_plot(df_scan_clt)

        return scan_clt_filename

    def gen_plot(self, df_scan_clt: pd.DataFrame) -> None:
        """Generate the scan plot based on provided data.
        Parameters
        ----------
        df_scan_clt : pd.DataFrame
            The data frame containing the data to be plotted.
        """
        if not self.generate_plot:
            return
        try:
            make_scan_plot(
                df_scan_clt,
                self.clt_id,
                self.scanned_residue,
                offline=self.offline,
                splitplot=self.splitplot,
                xaxis_title=self.plot_xaxis_title,
            )
        except Exception as e:
            log.warning(
                f"Could not create interactive plot. The following error occurred {e}"
            )


#: columns of the per-model scan TSV shared by single-residue scans
STANDARD_SCAN_COLUMNS = [
    "chain",
    "res",
    "ori_resname",
    "end_resname",
    "score",
    "vdw",
    "elec",
    "desolv",
    "bsa",
    "delta_score",
    "delta_vdw",
    "delta_elec",
    "delta_desolv",
    "delta_bsa",
]


def standard_scan_row(result: MutationResult) -> list:
    """Build a per-model TSV row for a single-residue mutation result."""
    m_score, m_vdw, m_elec, m_des, m_bsa = result.mutant_scores
    d_score, d_vdw, d_elec, d_des, d_bsa = result.delta_scores
    return [
        result.chain,
        result.resid,
        result.ori_resname,
        result.target_resname,
        m_score,
        m_vdw,
        m_elec,
        m_des,
        m_bsa,
        d_score,
        d_vdw,
        d_elec,
        d_des,
        d_bsa,
    ]


def write_scan_out(
    results: List[MutationResult],
    model_id: str,
    module_name: str,
    sort_columns: List[str],
    row_builder=standard_scan_row,
    columns: Optional[List[str]] = None,
    zscore_reference: str = "residues",
    extra_header_lines=(),
) -> None:
    """Save mutation results for one model to ``scan_{model_id}.tsv``.
    Parameters
    ----------
    results : List[MutationResult]
        List of mutation results from scanning.
    model_id : str
        Identifier for the model used in the filename.
    module_name : str
        Module label used in the file header (``alascan``/``rnascan``/...).
    sort_columns : List[str]
        Column names used to sort the rows.
    row_builder : callable
        Function mapping a successful ``MutationResult`` to a TSV row.
    columns : List[str], optional
        Column names of the rows; defaults to ``STANDARD_SCAN_COLUMNS``.
    zscore_reference : str
        Wording used in the z-score header comment (``residues``/``mutations``).
    extra_header_lines : iterable of str
        Extra comment lines added to the header (without the leading ``#``).
    Notes
    -----
    If ``results`` is empty, no file is created.
    """
    if not results:
        print(f"No scan results for model {model_id}")
        return

    if columns is None:
        columns = STANDARD_SCAN_COLUMNS

    scan_data = []
    native_score = None
    for result in results:
        if result.success:
            scan_data.append(row_builder(result))
            # Get native score from first result (mutant + delta = native)
            if native_score is None:
                native_score = result.mutant_scores[0] + result.delta_scores[0]

    if scan_data:
        df_scan = pd.DataFrame(scan_data, columns=columns)
        # Compute z-scores
        df_scan = add_zscores(df_scan, "delta_score")
        # Sort the rows
        df_scan.sort_values(by=sort_columns, inplace=True)
        # Get csv data as string
        csv_io = io.StringIO()
        df_scan.to_csv(csv_io, index=False, float_format="%.2f", sep="\t")
        csv_io.seek(0)
        # Save to tsv
        output_file = f"scan_{model_id}.tsv"
        with open(output_file, "w") as fout:
            fout.write(f"{'#' * 80}{os.linesep}")
            fout.write(f"# `{module_name}` results for {model_id}{os.linesep}")
            fout.write(f"#{os.linesep}")
            for extra in extra_header_lines:
                fout.write(f"# {extra}{os.linesep}")
            fout.write(f"# native score = {native_score}{os.linesep}")
            fout.write(f"#{os.linesep}")
            fout.write(
                f"# z_score is calculated with respect to the other "
                f"{zscore_reference}{os.linesep}"
            )
            fout.write(f"{'#' * 80}{os.linesep}")
            fout.write(csv_io.read())


def group_scan_by_cluster(
    models: List[PDBFile],
    results_by_model: Dict[str, List[MutationResult]],
    ident_builder,
    metadata_builder=None,
) -> Tuple[Dict[str, Dict[str, Dict[str, Union[float, int]]]], Dict[str, int]]:
    """Group per-model scan data per cluster.
    Parameters
    ----------
    models : List[PDBFile]
        List of input models.
    results_by_model : dict
        Mutation results keyed by model id.
    ident_builder : callable
        Function mapping a ``MutationResult`` to its unique string identifier.
    metadata_builder : callable, optional
        Function mapping a ``MutationResult`` to a dict of static metadata stored
        alongside the accumulated delta lists (used by paired-mutation modules).
    Returns
    -------
    clt_scan : dict
        Scan data for each cluster, grouped by mutation identifier.
    clt_pops : dict
        Number of entries for each cluster.
    """
    clt_scan: Dict[str, Dict[str, Dict[str, Union[float, int]]]] = {}
    clt_pops: Dict[str, int] = {}
    for model in models:
        cl_id = model.clt_id
        # unclustered models have cl_id = None
        if cl_id is None:
            cl_id = "unclustered"
        if cl_id not in clt_scan:
            clt_scan[cl_id] = {}
            clt_pops[cl_id] = 0
        clt_pops[cl_id] += 1
        model_id = model.file_name.removesuffix(".pdb")
        try:
            model_scan_dt = results_by_model[model_id]
        except KeyError:
            continue
        for mut_result in model_scan_dt:
            ident = ident_builder(mut_result)
            if ident not in clt_scan[cl_id]:
                entry: Dict[str, Union[float, int, list]] = {
                    "delta_score": [],
                    "delta_vdw": [],
                    "delta_elec": [],
                    "delta_desolv": [],
                    "delta_bsa": [],
                    "frac_pr": 0,
                }
                if metadata_builder is not None:
                    entry.update(metadata_builder(mut_result))
                clt_scan[cl_id][ident] = entry
            delta_scores = mut_result.delta_scores
            entry = clt_scan[cl_id][ident]
            entry["delta_score"].append(delta_scores[0])
            entry["delta_vdw"].append(delta_scores[1])
            entry["delta_elec"].append(delta_scores[2])
            entry["delta_desolv"].append(delta_scores[3])
            entry["delta_bsa"].append(delta_scores[4])
            entry["frac_pr"] += 1
    return clt_scan, clt_pops


# ---------------------------------------------------------------------------
# Shared interface-scan job infrastructure
# ---------------------------------------------------------------------------


class BaseInterfaceScanner:
    """Common state shared by every module's ``InterfaceScanner``.
    Subclasses add their own mutation target (e.g. ``mutation_res`` for alascan
    or ``scan_bases`` for the nucleic-acid modules) and implement ``run()``,
    which detects the interface and builds the module-specific mutation jobs.
    """

    def __init__(
        self,
        model: Union[str, Path, Any],
        params: Optional[Dict[str, Any]] = None,
    ) -> None:
        """Populate the attributes shared by all InterfaceScanner variants.
        Parameters
        ----------
        model : str, Path, or model object
            HADDOCK ``PDBFile`` model object or a path to a PDB file.
        params : dict, optional
            Module parameters (interface cutoff, chains, resdic filters,
            ligand topology/parameter files, ...).
        """
        self.model = model
        self.params = params or {}
        self.point_mutations_jobs: List[Any] = []
        self.ligand_param_fname = self.params.get("ligand_param_fname", "")
        self.ligand_top_fname = self.params.get("ligand_top_fname", "")
        self.filter_resdic = {
            key[-1]: value
            for key, value in self.params.items()
            if key.startswith("resdic")
        }
        if isinstance(model, PDBFile):
            self.model_path = model.rel_path
            self.model_id = model.file_name.removesuffix(".pdb")
        else:
            # model given as a plain path
            self.model_path = Path(model)
            self.model_id = self.model_path.stem


class ModelPointMutation:
    """Execute a single point mutation and score it against the native model.
    Shared by the alascan and rnascan modules, whose per-model scoring flow is
    identical; only the ``mutate`` primitive differs (protein residue vs RNA
    base). Each module keeps a thin ``run()`` that forwards its own module-level
    ``mutate`` and ``calc_score`` to :meth:`_run` (so both stay patchable in the
    module namespace for tests).
    """

    def __init__(
        self,
        model_path: Path,
        model_id: str,
        chain: str,
        resid: int,
        ori_resname: str,
        target_resname: str,
        native_scores: Tuple[float, float, float, float, float],
        output_mutants: bool = False,
        ligand_param_fname: Union[Path, str] = "",
        ligand_top_fname: Union[Path, str] = "",
    ) -> None:
        """Initialize a single point mutation job.
        Parameters
        ----------
        model_path : Path
            Path to the PDB file.
        model_id : str
            Identifier for the model.
        chain : str
            Chain identifier.
        resid : int
            Residue number.
        ori_resname : str
            Original residue name.
        target_resname : str
            Target residue/base name for the mutation.
        native_scores : tuple
            Native model scores (score, vdw, elec, desolv, bsa).
        output_mutants : bool
            Whether to keep the mutant PDB files.
        ligand_param_fname, ligand_top_fname : Union[Path, str]
            Additional CNS parameter/topology files.
        """
        self.model_path = Path(model_path)
        self.model_id = model_id
        self.chain = chain
        self.resid = resid
        self.ori_resname = ori_resname
        self.target_resname = target_resname
        self.native_scores = native_scores
        self.output_mutants = output_mutants
        self.ligand_param_fname = ligand_param_fname
        self.ligand_top_fname = ligand_top_fname

    def _run(self, mutate_func, calc_score_func) -> MutationResult:
        """Run the mutation with the given ``mutate``/``calc_score`` callables.
        Parameters
        ----------
        mutate_func : callable
            ``mutate(model_path, chain, resid, target_resname) -> Path`` that
            writes the mutated PDB and returns its path.
        calc_score_func : callable
            The module's ``calc_score`` (kept as an argument so it stays
            patchable in the module namespace during tests).
        """
        mutation_id = f"{self.model_id}_{self.chain}{self.resid}{self.target_resname}"

        try:
            # Setup working directory
            sc_dir = f"haddock3-score-{mutation_id}"
            os.makedirs(sc_dir, exist_ok=True)

            # Perform point mutation on pdb file
            mut_pdb = mutate_func(
                self.model_path, self.chain, self.resid, self.target_resname
            )

            # Calculate mutant scores
            mutant_scores = calc_score_func(
                mut_pdb,
                run_dir=sc_dir,
                outputpdb=self.output_mutants,
                ligand_param_fname=self.ligand_param_fname,
                ligand_top_fname=self.ligand_top_fname,
            )

            # Calculate deltas (native - mutant)
            n_score, n_vdw, n_elec, n_des, n_bsa = self.native_scores
            m_score, m_vdw, m_elec, m_des, m_bsa = mutant_scores
            delta_scores = (
                n_score - m_score,
                n_vdw - m_vdw,
                n_elec - m_elec,
                n_des - m_des,
                n_bsa - m_bsa,
            )

            # Handle output files
            em_mut_pdb = Path(f"{mut_pdb.stem}_hs.pdb")
            if not self.output_mutants:
                # if output_mutants = False, then remove both files
                if os.path.exists(mut_pdb):
                    os.remove(mut_pdb)
                if em_mut_pdb.exists():
                    os.remove(em_mut_pdb)
            else:
                # otherwise keep energy-minimized pdb
                if os.path.exists(em_mut_pdb):
                    shutil.move(em_mut_pdb, mut_pdb)
            # clean up scoring dir
            if os.path.exists(sc_dir):
                shutil.rmtree(sc_dir)

            return MutationResult(
                model_id=self.model_id,
                chain=self.chain,
                resid=self.resid,
                ori_resname=self.ori_resname,
                target_resname=self.target_resname,
                mutant_scores=mutant_scores,
                delta_scores=delta_scores,
                success=True,
            )

        except Exception as e:
            return MutationResult(
                model_id=self.model_id,
                chain=self.chain,
                resid=self.resid,
                ori_resname=self.ori_resname,
                target_resname=self.target_resname,
                mutant_scores=(0, 0, 0, 0, 0),
                delta_scores=(0, 0, 0, 0, 0),
                success=False,
                error_msg=str(e),
            )