OST Actions¶

usage: ost compare-structures [-h] -m MODEL -r REFERENCE [-o OUTPUT]
                              [-mf {pdb,cif,mmcif}] [-rf {pdb,cif,mmcif}]
                              [-mb MODEL_BIOUNIT] [-rb REFERENCE_BIOUNIT]
                              [-rna] [-ec] [-d] [-ds DUMP_SUFFIX] [-ft]
                              [-c CHAIN_MAPPING [CHAIN_MAPPING ...]] [--lddt]
                              [--local-lddt] [--bb-lddt] [--bb-local-lddt]
                              [--cad-score] [--local-cad-score]
                              [--cad-exec CAD_EXEC]
                              [--usalign-exec USALIGN_EXEC] [--qs-score]
                              [--dockq] [--contact-scores] [--rigid-scores]
                              [--patch-scores] [--tm-score]
                              [--lddt-no-stereochecks]
                              [--n-max-naive N_MAX_NAIVE]

Evaluate model against reference

Example: ost compare-structures -m model.pdb -r reference.cif

Loads the structures and performs basic cleanup:

 * Assign elements according to the PDB Chemical Component Dictionary
 * Map nonstandard residues to their parent residues as defined by the PDB
   Chemical Component Dictionary, e.g. phospho-serine => serine
 * Remove hydrogens
 * Remove OXT atoms
 * Remove unknown atoms, i.e. atoms that are not expected according to the PDB
   Chemical Component Dictionary
 * Select for peptide/nucleotide residues

The cleaned structures are optionally dumped using -d/--dump-structures

Output is written in JSON format (default: out.json). In case of no additional
options, this is a dictionary with 8 keys describing model/reference comparison:

 * "reference_chains": Chain names of reference
 * "model_chains": Chain names of model
 * "chem_groups": Groups of polypeptides/polynucleotides from reference that
   are considered chemically equivalent. You can derive stoichiometry from this.
   Contains only chains that are considered in chain mapping, i.e. pass a
   size threshold (defaults: 10 for peptides, 4 for nucleotides).
 * "chem_mapping": List of same length as "chem_groups". Assigns model chains to
   the respective chem group. Again, only contains chains that are considered
   in chain mapping.
 * "chain_mapping": A dictionary with reference chain names as keys and the
   mapped model chain names as values. Missing chains are either not mapped
   (but present in "chem_groups", "chem_mapping") or were not considered in
   chain mapping (short peptides etc.)
 * "aln": Pairwise sequence alignment for each pair of mapped chains in fasta
   format.
 * "inconsistent_residues": List of strings that represent name mismatches of
   aligned residues in form
   <trg_cname>.<trg_rnum>.<trg_ins_code>-<mdl_cname>.<mdl_rnum>.<mdl_ins_code>.
   Inconsistencies may lead to corrupt results but do not abort the program.
   Program abortion in these cases can be enforced with
   -ec/--enforce-consistency.
 * "status": SUCCESS if everything ran through. In case of failure, the only
   content of the JSON output will be "status" set to FAILURE and an
   additional key: "traceback".

The following additional keys store relevant input parameters to reproduce
results:

 * "model"
 * "reference"
 * "fault_tolerant"
 * "model_biounit"
 * "reference_biounit"
 * "residue_number_alignment"
 * "enforce_consistency"
 * "cad_exec"
 * "usalign_exec"
 * "lddt_no_stereochecks"

The pairwise sequence alignments are computed with Needleman-Wunsch using
BLOSUM62 (NUC44 for nucleotides). Many benchmarking scenarios preprocess the
structures to ensure matching residue numbers (CASP/CAMEO). In these cases,
enabling -rna/--residue-number-alignment is recommended.

Each score is opt-in and can be enabled with optional arguments.

Example to compute global and per-residue lDDT values as well as QS-score:

ost compare-structures -m model.pdb -r reference.cif --lddt --local-lddt --qs-score

Example to inject custom chain mapping

ost compare-structures -m model.pdb -r reference.cif -c A:B B:A

optional arguments:
  -h, --help            show this help message and exit
  -m MODEL, --model MODEL
                        Path to model file.
  -r REFERENCE, --reference REFERENCE
                        Path to reference file.
  -o OUTPUT, --output OUTPUT
                        Output file name. The output will be saved as a JSON
                        file. default: out.json
  -mf {pdb,cif,mmcif}, --model-format {pdb,cif,mmcif}
                        Format of model file. pdb reads pdb but also pdb.gz,
                        same applies to cif/mmcif. Inferred from filepath if
                        not given.
  -rf {pdb,cif,mmcif}, --reference-format {pdb,cif,mmcif}
                        Format of reference file. pdb reads pdb but also
                        pdb.gz, same applies to cif/mmcif. Inferred from
                        filepath if not given.
  -mb MODEL_BIOUNIT, --model-biounit MODEL_BIOUNIT
                        Only has an effect if model is in mmcif format. By
                        default, the asymmetric unit (AU) is used for scoring.
                        If there are biounits defined in the mmcif file, you
                        can specify the (0-based) index of the one which
                        should be used.
  -rb REFERENCE_BIOUNIT, --reference-biounit REFERENCE_BIOUNIT
                        Only has an effect if reference is in mmcif format. By
                        default, the asymmetric unit (AU) is used for scoring.
                        If there are biounits defined in the mmcif file, you
                        can specify the (0-based) index of the one which
                        should be used.
  -rna, --residue-number-alignment
                        Make alignment based on residue number instead of
                        using a global BLOSUM62-based alignment (NUC44 for
                        nucleotides).
  -ec, --enforce-consistency
                        Enforce consistency. By default residue name
                        discrepancies between a model and reference are
                        reported but the program proceeds. If this flag is ON,
                        the program fails for these cases.
  -d, --dump-structures
                        Dump cleaned structures used to calculate all the
                        scores as PDB files using specified suffix. Files will
                        be dumped to the same location as original files.
  -ds DUMP_SUFFIX, --dump-suffix DUMP_SUFFIX
                        Use this suffix to dump structures. Defaults to
                        .compare.structures.pdb.
  -ft, --fault-tolerant
                        Fault tolerant parsing.
  -c CHAIN_MAPPING [CHAIN_MAPPING ...], --chain-mapping CHAIN_MAPPING [CHAIN_MAPPING ...]
                        Custom mapping of chains between the reference and the
                        model. Each separate mapping consist of key:value
                        pairs where key is the chain name in reference and
                        value is the chain name in model.
  --lddt                Compute global lDDT score with default
                        parameterization and store as key "lddt".
                        Stereochemical irregularities affecting lDDT are
                        reported as keys "model_clashes", "model_bad_bonds",
                        "model_bad_angles" and the respective reference
                        counterparts.
  --local-lddt          Compute per-residue lDDT scores with default
                        parameterization and store as key "local_lddt". Score
                        for each residue is accessible by key
                        <chain_name>.<resnum>.<resnum_inscode>. Residue with
                        number 42 in chain X can be extracted with:
                        data["local_lddt"]["X.42."]. If there is an insertion
                        code, lets say A, the residue key becomes "X.42.A".
                        Stereochemical irregularities affecting lDDT are
                        reported as keys "model_clashes", "model_bad_bonds",
                        "model_bad_angles" and the respective reference
                        counterparts. Atoms specified in there follow the
                        following format:
                        <chain_name>.<resnum>.<resnum_inscode>.<atom_name>
  --bb-lddt             Compute global lDDT score with default
                        parameterization and store as key "bb_lddt". lDDT in
                        this case is only computed on backbone atoms: CA for
                        peptides and C3' for nucleotides
  --bb-local-lddt       Compute per-residue lDDT scores with default
                        parameterization and store as key "bb_local_lddt".
                        lDDT in this case is only computed on backbone atoms:
                        CA for peptides and C3' for nucleotides. Per-residue
                        scores are accessible as described for local_lddt.
  --cad-score           Compute global CAD's atom-atom (AA) score and store as
                        key "cad_score". --residue-number-alignment must be
                        enabled to compute this score. Requires
                        voronota_cadscore executable in PATH. Alternatively
                        you can set cad-exec.
  --local-cad-score     Compute local CAD's atom-atom (AA) scores and store as
                        key "local_cad_score". Per-residue scores are
                        accessible as described for local_lddt. --residue-
                        number-alignments must be enabled to compute this
                        score. Requires voronota_cadscore executable in PATH.
                        Alternatively you can set cad-exec.
  --cad-exec CAD_EXEC   Path to voronota-cadscore executable (installed from
                        https://github.com/kliment-olechnovic/voronota).
                        Searches PATH if not set.
  --usalign-exec USALIGN_EXEC
                        Path to USalign executable to compute TM-score. If not
                        given, an OpenStructure internal copy of USalign code
                        is used.
  --qs-score            Compute QS-score, stored as key "qs_global", and the
                        QS-best variant, stored as key "qs_best". Interfaces
                        in the reference with non-zero contribution to QS-
                        score are available as key "qs_reference_interfaces",
                        the ones from the model as key "qs_model_interfaces".
                        "qs_interfaces" is a subset of
                        "qs_reference_interfaces" that contains interfaces
                        that can be mapped to the model. They are stored as
                        lists in format [ref_ch1, ref_ch2, mdl_ch1, mdl_ch2].
                        The respective per-interface scores for
                        "qs_interfaces" are available as keys
                        "per_interface_qs_global" and "per_interface_qs_best"
  --dockq               Compute DockQ scores and its components. Relevant
                        interfaces with at least one contact (any atom within
                        5A) of the reference structure are available as key
                        "dockq_reference_interfaces". Only interfaces between
                        peptide chains are considered here! Key
                        "dockq_interfaces" is a subset of
                        "dockq_reference_interfaces" that contains interfaces
                        that can be mapped to the model. They are stored as
                        lists in format [ref_ch1, ref_ch2, mdl_ch1, mdl_ch2].
                        The respective DockQ scores for "dockq_interfaces" are
                        available as key "dockq". It's components are
                        available as keys: "fnat" (fraction of reference
                        contacts which are also there in model) "irmsd"
                        (interface RMSD), "lrmsd" (ligand RMSD). The DockQ
                        score is strictly designed to score each interface
                        individually. We also provide two averaged versions to
                        get one full model score: "dockq_ave", "dockq_wave".
                        The first is simply the average of "dockq_scores", the
                        latter is a weighted average with weights derived from
                        number of contacts in the reference interfaces. These
                        two scores only consider interfaces that are present
                        in both, the model and the reference. "dockq_ave_full"
                        and "dockq_wave_full" add zeros in the average
                        computation for each interface that is only present in
                        the reference but not in the model.
  --ics                 Computes interface contact similarity (ICS) related
                        scores. A contact between two residues of different
                        chains is defined as having at least one heavy atom
                        within 5A. Contacts in reference structure are
                        available as key "reference_contacts". Each contact
                        specifies the interacting residues in format
                        "<cname>.<rnum>.<ins_code>". Model contacts are
                        available as key "model_contacts". The precision which
                        is available as key "ics_precision" reports the
                        fraction of model contacts that are also present in
                        the reference. The recall which is available as key
                        "ics_recall" reports the fraction of reference
                        contacts that are correctly reproduced in the model.
                        The ICS score (Interface Contact Similarity) available
                        as key "ics" combines precision and recall using the
                        F1-measure. All these measures are also available on a
                        per-interface basis for each interface in the
                        reference structure that are defined as chain pairs
                        with at least one contact (available as key
                        "contact_reference_interfaces"). The respective
                        metrics are available as keys
                        "per_interface_ics_precision",
                        "per_interface_ics_recall" and "per_interface_ics".
  --ips                 Computes interface patch similarity (IPS) related
                        scores. They focus on interface residues. They are
                        defined as having at least one contact to a residue
                        from any other chain. In short: if they show up in the
                        contact lists used to compute ICS. If ips is enabled,
                        these contacts get reported too and are available as
                        keys "reference_contacts" and "model_contacts".The
                        precision which is available as key "ips_precision"
                        reports the fraction of model interface residues, that
                        are also interface residues in the reference. The
                        recall which is available as key "ips_recall" reports
                        the fraction of reference interface residues that are
                        also interface residues in the model. The IPS score
                        (Interface Patch Similarity) available as key "ips" is
                        the Jaccard coefficient between interface residues in
                        reference and model. All these measures are also
                        available on a per-interface basis for each interface
                        in the reference structure that are defined as chain
                        pairs with at least one contact (available as key
                        "contact_reference_interfaces"). The respective
                        metrics are available as keys
                        "per_interface_ips_precision",
                        "per_interface_ips_recall" and "per_interface_ips".
  --rigid-scores        Computes rigid superposition based scores. They're
                        based on a Kabsch superposition of all mapped CA
                        positions (C3' for nucleotides). Makes the following
                        keys available: "oligo_gdtts": GDT with distance
                        thresholds [1.0, 2.0, 4.0, 8.0] given these positions
                        and transformation, "oligo_gdtha": same with
                        thresholds [0.5, 1.0, 2.0, 4.0], "rmsd": RMSD given
                        these positions and transformation, "transform": the
                        used 4x4 transformation matrix that superposes model
                        onto reference.
  --patch-scores        Local interface quality score used in CASP15. Scores
                        each model residue that is considered in the interface
                        (CB pos within 8A of any CB pos from another chain (CA
                        for GLY)). The local neighborhood gets represented by
                        "interface patches" which are scored with QS-score and
                        DockQ. Scores where not the full patches are
                        represented by the reference are set to None. Model
                        interface residues are available as key
                        "model_interface_residues", reference interface
                        residues as key "reference_interface_residues".
                        Residues are represented as string in form
                        <chain_name>.<resnum>.<resnum_inscode>. The respective
                        scores are available as keys "patch_qs" and
                        "patch_dockq"
  --tm-score            Computes TM-score with the USalign tool. Also computes
                        a chain mapping in case of complexes that is stored in
                        the same format as the default mapping. TM-score and
                        the mapping are available as keys "tm_score" and
                        "usalign_mapping"
  --lddt-no-stereochecks
                        Disable stereochecks for lDDT computation
  --n-max-naive N_MAX_NAIVE
                        Parameter for chain mapping. If the number of possible
                        mappings is <= *n_max_naive*, the full mapping
                        solution space is enumerated to find the the mapping
                        with optimal QS-score. A heuristic is used otherwise.
                        The default of 40320 corresponds to an octamer (8! =
                        40320). A structure with stoichiometry A6B2 would be
                        6!*2! = 1440 etc.
  --dump-aligned-residues
                        Dump additional info on aligned model and reference
                        residues.
  --dump-pepnuc-alns    Dump alignments of mapped chains but with sequences
                        that did not undergo Molck preprocessing in the
                        scorer. Sequences are extracted from model/target
                        after undergoing selection for peptide and nucleotide
                        residues.
  --dump-pepnuc-aligned-residues
                        Dump additional info on model and reference residues
                        that occur in pepnuc alignments.

usage: ost compare-ligand-structures [-h] -m MODEL [-ml [MODEL_LIGANDS ...]]
                                     -r REFERENCE [-rl [REFERENCE_LIGANDS ...]]
                                     [-o OUTPUT] [-mf {pdb,mmcif,cif}]
                                     [-rf {pdb,mmcif,cif}] [-ft] [-rna] [-ec] [-sm]
                                     [-gcm] [-c CHAIN_MAPPING [CHAIN_MAPPING ...]]
                                     [-ra] [--lddt-pli] [--rmsd] [--radius RADIUS]
                                     [--lddt-pli-radius LDDT_PLI_RADIUS]
                                     [--lddt-lp-radius LDDT_LP_RADIUS]
                                     [-v VERBOSITY] [--n-max-naive N_MAX_NAIVE]

Evaluate model with non-polymer/small molecule ligands against reference.

Example: ost compare-ligand-structures \
    -m model.pdb \
    -ml ligand.sdf \
    -r reference.cif \
    --lddt-pli --rmsd

Structures of polymer entities (proteins and nucleotides) can be given in PDB
or mmCIF format. If the structure is given in mmCIF format, only the asymmetric
unit (AU) is used for scoring.

Ligands can be given as path to SDF files containing the ligand for both model
(--model-ligands/-ml) and reference (--reference-ligands/-rl). If omitted,
ligands will be detected in the model and reference structures. For structures
given in mmCIF format, this is based on the annotation as "non polymer entity"
(i.e. ligands in the _pdbx_entity_nonpoly mmCIF category) and works reliably.
For structures given in PDB format, this is based on the HET records and is
normally not what you want. You should always give ligands as SDF for
structures in PDB format.

Polymer/oligomeric ligands (saccharides, peptides, nucleotides) are not
supported.

Only minimal cleanup steps are performed (remove hydrogens, and for structures
of polymers only, remove unknown atoms and cleanup element column).

Ligands in mmCIF and PDB files must comply with the PDB component dictionary
definition, and have properly named residues and atoms, in order for
ligand connectivity to be loaded correctly. Ligands loaded from SDF files
are exempt from this restriction, meaning any arbitrary ligand can be assessed.

Output is written in JSON format (default: out.json). In case of no additional
options, this is a dictionary with three keys:

 * "model_ligands": A list of ligands in the model. If ligands were provided
   explicitly with --model-ligands, elements of the list will be the paths to
   the ligand SDF file(s). Otherwise, they will be the chain name, residue
   number and insertion code of the ligand, separated by a dot.
 * "reference_ligands": A list of ligands in the reference. If ligands were
   provided explicitly with --reference-ligands, elements of the list will be
   the paths to the ligand SDF file(s). Otherwise, they will be the chain name,
   residue number and insertion code of the ligand, separated by a dot.
 * "status": SUCCESS if everything ran through. In case of failure, the only
   content of the JSON output will be "status" set to FAILURE and an
   additional key: "traceback".

Each score is opt-in and, be enabled with optional arguments and is added
to the output. Keys correspond to the values in "model_ligands" above.
Unassigned ligands are reported with a message in
"unassigned_model_ligands" and "unassigned_reference_ligands".

options:
  -h, --help            show this help message and exit
  -m MODEL, --mdl MODEL, --model MODEL
                        Path to model file.
  -ml [MODEL_LIGANDS ...], --mdl-ligands [MODEL_LIGANDS ...],
                        --model-ligands [MODEL_LIGANDS ...]
                        Path to model ligand files.
  -r REFERENCE, --ref REFERENCE, --reference REFERENCE
                        Path to reference file.
  -rl [REFERENCE_LIGANDS ...], --ref-ligands [REFERENCE_LIGANDS ...],
                        --reference-ligands [REFERENCE_LIGANDS ...]
                        Path to reference ligand files.
  -o OUTPUT, --out OUTPUT, --output OUTPUT
                        Output file name. The output will be saved as a JSON
                        file. default: out.json
  -mf {pdb,mmcif,cif}, --mdl-format {pdb,mmcif,cif},
                        --model-format {pdb,mmcif,cif}
                        Format of model file. Inferred from path if not
                        given.
  -rf {pdb,mmcif,cif}, --reference-format {pdb,mmcif,cif},
                        --ref-format {pdb,mmcif,cif}
                        Format of reference file. Inferred from path if not
                        given.
  -ft, --fault-tolerant
                        Fault tolerant parsing.
  -rna, --residue-number-alignment
                        Make alignment based on residue number instead of
                        using a global BLOSUM62-based alignment (NUC44 for
                        nucleotides).
  -ec, --enforce-consistency
                        Enforce consistency of residue names between the
                        reference binding site and the model. By default
                        residue name discrepancies are reported but the
                        program proceeds. If this is set to True, the program
                        will fail with an error message if the residues names
                        differ. Note: more binding site mappings may be
                        explored during scoring, but only inconsistencies in
                        the selected mapping are reported.
  -sm, --substructure-match
                        Allow incomplete target ligands.
  -gcm, --global-chain-mapping
                        Use a global chain mapping.
  -c CHAIN_MAPPING [CHAIN_MAPPING ...],
                        --chain-mapping CHAIN_MAPPING [CHAIN_MAPPING ...]
                        Custom mapping of chains between the reference and
                        the model. Each separate mapping consist of key:value
                        pairs where key is the chain name in reference and
                        value is the chain name in model. Only has an effect
                        if global-chain-mapping flag is set.
  -ra, --rmsd-assignment
                        Use RMSD for ligand assignment.
  -u, --unassigned      Report unassigned model ligands in the output
                        together with assigned ligands, with a null score,
                        and reason for not being assigned.

  --lddt-pli            Compute lDDT-PLI score and store as key "lddt-pli".
  --rmsd                Compute RMSD score and store as key "rmsd".
  --radius RADIUS       Inclusion radius for the binding site. Any residue
                        with atoms within this distance of the ligand will
                        be included in the binding site.
  --lddt-pli-radius LDDT_PLI_RADIUS
                        lDDT inclusion radius for lDDT-PLI.
  --lddt-lp-radius LDDT_LP_RADIUS
                        lDDT inclusion radius for lDDT-LP.
  -v VERBOSITY, --verbosity VERBOSITY
                        Set verbosity level. Defaults to 3 (INFO).
  --n-max-naive N_MAX_NAIVE
                        If number of chains in model and reference are
                        below or equal that number, the global chain
                        mapping will naively enumerate all possible
                        mappings. A heuristic is used otherwise.