Blame for scripts/ssp_lib.py

"""Shared helpers for building SSP (secondary structure datasets), versions `rcsb` and `casp`."""
import os, re, glob, gzip, html, json, time, tempfile, subprocess, urllib.request
import gemmi
from Bio import Align
from Bio.Align import substitution_matrices

TMP = os.environ.get("SS_TMP", tempfile.gettempdir())
SS8_TO_SS3 = {"G": "H", "H": "H", "I": "H", "B": "E", "E": "E", "S": "C", "T": "C", "C": "C"}
ATOMS = ("N", "CA", "C", "O", "CB")
DSSP_VERSION = subprocess.run(["mkdssp", "--version"], capture_output=True, text=True).stdout.strip()

# ----------------------------------------------------------------------------------------------------- CASP pages
def listed_targets(casp_dir):
    """Live (not canceled) targets on CASP's target list -> sorted list of PDB codes CASP gives (may be empty)."""
    page = open(f"{casp_dir}/targetlist.html", errors="ignore").read()
    out = {}
    for p in re.split(r'(?=<td[^>]*>\s*(?:<[^>]+>\s*)*T\d{4}[A-Za-z0-9_]*\s*<)', page)[1:]:
        m = re.match(r'<td[^>]*>\s*(?:<[^>]+>\s*)*(T\d{4}[A-Za-z0-9_]*)\s*<', p)
        if not m:
            continue
        row = p.split("</tr>")[0]
        text = re.sub(r"\s+", " ", html.unescape(re.sub(r"<[^>]+>", " ", row)))
        if "canceled" in text.lower():
            continue
        codes = set(x.lower() for x in re.findall(r"rcsb\.org/[^\"']*?([0-9][A-Za-z0-9]{3})\b", row))
        codes |= set(x.lower() for x in re.findall(r"PDB code\s+([0-9][A-Za-z0-9]{3})\b", text))
        out[m.group(1)] = sorted(codes)
    return out


def _read_fasta(path, into):
    cur = None
    for line in open(path):
        line = line.strip()
        if line.startswith(">"):
            cur = line[1:].split()[0]; into[cur] = ""
        elif cur:
            into[cur] += line


def target_sequences(rnd, casp_dir, needed):
    """CASP target sequences: the round's *.seq.txt files, then per-target pages (cached) for anything missing."""
    seqs = {}
    for f in sorted(glob.glob(f"{casp_dir}/*.seq.txt")):
        if not f.endswith("target_pages.seq.txt"):
            _read_fasta(f, seqs)
    cache = f"{casp_dir}/target_pages.seq.txt"
    if os.path.exists(cache):
        _read_fasta(cache, seqs)
    missing = [t for t in needed if t not in seqs]
    if missing:
        with open(cache, "a") as out:
            for t in missing:
                txt = urllib.request.urlopen(f"https://predictioncenter.org/casp{rnd}/target.cgi?target={t}&view=sequence",
                                             timeout=60).read().decode(errors="ignore")
                lines = [l.strip() for l in txt.splitlines() if l.strip()]
                if lines and lines[0].startswith(">"):
                    seqs[t] = "".join(l for l in lines[1:] if not l.startswith(">"))
                    out.write(f">{t}\n{seqs[t]}\n")
                time.sleep(0.2)
    return seqs


# ----------------------------------------------------------------------------------------------------- matching
_al = Align.PairwiseAligner(mode="local", substitution_matrix=substitution_matrices.load("BLOSUM62"),
                            open_gap_score=-11, extend_gap_score=-1)


def pieces(t, p, minlen=8):
    """t as separate, non-overlapping exact stretches of p in chain order -> [(t0,t1,p0,p1)], or None."""
    out, i, pos = [], 0, 0
    while i < len(t):
        for L in range(len(t) - i, minlen - 1, -1):
            j = p.find(t[i:i + L], pos)
            if j >= 0:
                out.append((i, i + L, j, j + L)); i += L; pos = j + L; break
        else:
            return None
    return out


def match(target, chain_seq):
    """How a CASP target sequence relates to a chain sequence.
    Returns (category, fraction of target residues identical, regions as 1-based [start, end] in the chain or None)."""
    if target == chain_seq:
        return "byte-identical", 1.0, [[1, len(chain_seq)]]
    j = chain_seq.find(target)
    if j >= 0:
        return "contained", 1.0, [[j + 1, j + len(target)]]
    segs = pieces(target, chain_seq)
    if segs:
        return "pieces", 1.0, [[c + 1, d] for a, b, c, d in segs]
    try:
        aln = _al.align(target, chain_seq)[0]
    except IndexError:
        return "differs", 0.0, None
    same = sum(target[i] == chain_seq[j] for (a0, a1), (b0, b1) in zip(*aln.aligned)
               for i, j in zip(range(a0, a1), range(b0, b1)))
    return "differs", round(same / len(target), 4), None


# ----------------------------------------------------------------------------------------------------- RCSB
def post(url, payload):
    req = urllib.request.Request(url, data=json.dumps(payload).encode(), headers={"Content-Type": "application/json"})
    with urllib.request.urlopen(req, timeout=180) as r:
        return json.loads(r.read())


def entry_info(codes, cache_path):
    """Per entry: release date, method(s), resolution, and protein entities (canonical sequence, author chains)."""
    os.makedirs(os.path.dirname(cache_path), exist_ok=True)
    cache = json.load(open(cache_path)) if os.path.exists(cache_path) else {}
    todo = sorted({c.upper() for c in codes} - set(cache))
    gql = """query($ids:[String!]!){ entries(entry_ids:$ids){ rcsb_id rcsb_accession_info{ initial_release_date }
      exptl{ method } rcsb_entry_info{ resolution_combined }
      polymer_entities{ rcsb_id entity_poly{ pdbx_seq_one_letter_code_can rcsb_entity_polymer_type }
        rcsb_polymer_entity_container_identifiers{ auth_asym_ids } } } }"""
    for k in range(0, len(todo), 50):
        got = post("https://data.rcsb.org/graphql", {"query": gql, "variables": {"ids": todo[k:k + 50]}})["data"]["entries"] or []
        found = {e["rcsb_id"] for e in got}
        for e in got:
            cache[e["rcsb_id"]] = {
                "release_date": e["rcsb_accession_info"]["initial_release_date"][:10],
                "method": "; ".join(x["method"] for x in e["exptl"]),
                "resolution": (e["rcsb_entry_info"].get("resolution_combined") or [None])[0],
                "entities": [{"entity": pe["rcsb_id"], "sequence": pe["entity_poly"]["pdbx_seq_one_letter_code_can"].replace("\n", ""),
                              "chains": pe["rcsb_polymer_entity_container_identifiers"]["auth_asym_ids"]}
                             for pe in e["polymer_entities"] or [] if pe["entity_poly"]["rcsb_entity_polymer_type"] == "Protein"]}
        for c in set(todo[k:k + 50]) - found:
            cache[c] = None  # not available from RCSB (e.g. obsoleted or never released)
    json.dump(cache, open(cache_path, "w"), indent=1)
    return {c.lower(): cache[c.upper()] for c in codes}


def download_cif(code, cache_dir):
    os.makedirs(cache_dir, exist_ok=True)
    path = f"{cache_dir}/{code}.cif.gz"
    if not os.path.exists(path):
        urllib.request.urlretrieve(f"https://files.rcsb.org/download/{code}.cif.gz", path)
    return path


def latest_revision(cif_path):
    block = gemmi.cif.read(cif_path).sole_block()
    dates = [gemmi.cif.as_string(d) for d in block.find_values("_pdbx_audit_revision_history.revision_date")]
    return max(dates) if dates else None


def clean(st):
    st.setup_entities()
    st.remove_hydrogens()
    st.remove_alternative_conformations()  # keeps the first conformer
    st.remove_ligands_and_waters()
    return st


def rcsb_chain(cif_path, chain_name):
    """Canonical sequence of the chain's entity and {1-based position: residue} for its observed residues."""
    st = clean(gemmi.read_structure(cif_path))
    poly = st[0][chain_name].get_polymer()
    ent = st.get_entity_of(poly)
    block = gemmi.cif.read(cif_path).sole_block()
    can = None
    for row in block.find("_entity_poly.", ["entity_id", "pdbx_seq_one_letter_code_can"]):
        if gemmi.cif.as_string(row[0]) == ent.name:
            can = gemmi.cif.as_string(row[1]).replace("\n", "").replace(" ", "")
    if can is None or len(can) != len(ent.full_sequence):
        raise ValueError(f"canonical sequence of entity {ent.name} does not line up with its monomer list")
    residues = {r.label_seq: r for r in poly if r.label_seq is not None}
    return st, can, residues


# ----------------------------------------------------------------------------------------------------- CASP files
def casp_chain(paths, target_seq):
    """Merge one or more CASP target files (domain pieces of one target) into {position: residue}; residue numbers in
    CASP target files are 1-based positions in the target sequence. Returns (structure, residues, name mismatches)."""
    residues = {}
    keep = None
    for p in paths:
        st = clean(gemmi.read_structure(p))
        keep = keep or st
        for r in st[0][0]:
            residues.setdefault(r.seqid.num, r)
    mism = [(n, r.name) for n, r in residues.items()
            if not (0 < n <= len(target_seq)) or _one(r.name) != target_seq[n - 1]]
    return keep, residues, mism


def _one(resname):
    t = gemmi.find_tabulated_residue(resname)
    return t.one_letter_code.upper() if t and t.one_letter_code.strip() and t.one_letter_code != "?" else "X"


# ----------------------------------------------------------------------------------------------------- DSSP
def dssp(residues, cell=None):
    """Run mkdssp on the given residues as one chain (residue number = position). Returns
    {position: (ss8_pp letter, classic ss8 letter)} and counts of how polyproline residues were resolved."""
    ns = gemmi.Structure()
    if cell is not None:
        ns.cell = cell
    m, ch = gemmi.Model("1"), gemmi.Chain("A")
    for pos in sorted(residues):
        ch.add_residue(residues[pos])
        ch[len(ch) - 1].seqid = gemmi.SeqId(pos, " ")
    m.add_chain(ch)
    ns.add_model(m)
    ns.setup_entities()
    fd, pdb = tempfile.mkstemp(suffix=".pdb", dir=TMP)
    os.close(fd)
    out = pdb[:-4] + ".dssp"
    try:
        ns.write_pdb(pdb)
        subprocess.run(["mkdssp", "--output-format", "dssp", pdb, out], check=True, capture_output=True)
        lines = open(out).read().splitlines()
    finally:
        for p in (pdb, out):
            if os.path.exists(p):
                os.remove(p)
    start = next(i for i, l in enumerate(lines) if l.startswith("  #  RESIDUE"))
    recs = [l for l in lines[start + 1:] if l[13] != "!"]
    # residues inside an n-turn (n = 3, 4, 5), from the turn-start markers ('>' or 'X') in columns 19-21
    in_turn = [False] * len(recs)
    for k, l in enumerate(recs):
        for n, col in ((3, 18), (4, 19), (5, 20)):
            if l[col] in ">X":
                for j in range(k + 1, min(k + n, len(recs))):
                    in_turn[j] = True
    bad = [l for k, l in enumerate(recs) if l[16] == "T" and not in_turn[k]]
    if bad:
        raise RuntimeError(f"DSSP column reading is wrong: {len(bad)} residues DSSP calls T are not inside a turn")
    labels, pp = {}, {"P_total": 0, "P_was_turn": 0, "P_was_bend": 0}
    for k, l in enumerate(recs):
        pos, s = int(l[5:10]), l[16]
        s = "C" if s == " " else s
        classic = s
        if s == "P":  # DSSP 4 polyproline; classic DSSP (no P) would give T, S or coil here
            pp["P_total"] += 1
            if in_turn[k]:
                classic = "T"; pp["P_was_turn"] += 1
            elif l[21] == "S":
                classic = "S"; pp["P_was_bend"] += 1
            else:
                classic = "C"
        labels[pos] = (s, classic)
    return labels, pp


def label_strings(length, labels):
    """Label strings plus the `resolved` mask. As in NetSurfP-2.0/TAPE, a residue DSSP gives no label (missing from the
    structure, or backbone incomplete) is labelled C and gets resolved = 0 (TAPE's `disorder` = 0)."""
    pos = range(1, length + 1)
    resolved = [1 if i in labels else 0 for i in pos]
    ss8_pp = "".join(labels[i][0] if i in labels else "C" for i in pos)
    ss8 = "".join(labels[i][1] if i in labels else "C" for i in pos)
    ss3 = "".join(SS8_TO_SS3[c] for c in ss8)
    return ss3, ss8, ss8_pp, resolved


def coordinates(length, residues):
    """Per atom name: list over positions of [x, y, z] or None (residue missing, or atom absent e.g. CB of glycine)."""
    out = {a: [None] * length for a in ATOMS}
    for pos, r in residues.items():
        if not 0 < pos <= length:
            continue
        for a in ATOMS:
            at = r.find_atom(a, "*")
            if at is not None:
                out[a][pos - 1] = [round(at.pos.x, 3), round(at.pos.y, 3), round(at.pos.z, 3)]
    return out