Add cofactor-EC coverage as a second, independent cognate-ligand source

[m-crown]

Summary

• Closes the cofactor coverage gap described in docs/cofactor_coverage_plan.md: cognate ligands were previously derived only from reaction equations, which structurally misses catalytic/prosthetic cofactors that never appear as a reactant/product (e.g. NAD, FAD, PLP, metal centers).
• Adds a second, independent source: CoFactor DB 2010 + BRENDA (vendored from RelLig's cofactor_ec.csv/cofactors_details.json) combined with UniProt's structured COFACTOR annotations, built into cofactor_ligands_df.pkl by new nextflow/bin/preprocess_cofactors.py (mirrors preprocess_rhea.py's pattern).
• get_ec_information.py concats this alongside the existing reaction-derived sources into cognate_ligands_df, tagged via a new ligand_source column (reaction / cofactor, unioned when both apply). Strict addition - existing reaction-derived rows are unaffected (verified by test).
• Partial ECs from UniProt are handled per the plan's broadcast rule: subsubclass-level wildcards (N.N.N.-) are expanded to matching terminal ECs; class/subclass-level wildcards are dropped rather than broadcast (confirmed during planning that broadcasting those produces nonsense - e.g. a class-level wildcard matching literally every terminal EC in that class).
• get_chem_comp_descriptors moved from process_all_pdb_contacts.py into utils.py so both scripts can share the CCD→SMILES resolution logic.
• reference_data_manifest.yaml updated: removed the stale RelLig bulk-TSV entries from an earlier version of the plan (checked against the real files - no EC column in either), added the three sources actually used, all optional and URL-verified.

Test plan

• nextflow/bin/tests/test_preprocess_cofactors.py - 21 tests covering UniProt parsing, the EC-completeness/broadcast safety rule (including a regression test for the class-level-wildcard bug caught during planning), CoFactor DB table loading, ChEBI resolution, and end-to-end build_cofactor_ligands_df.
• nextflow/bin/tests/test_utils_ec_broadcast.py - 10 tests for classify_ec_completeness, broadcast_subsubclass_ec, and the moved get_chem_comp_descriptors.
• nextflow/bin/tests/test_get_ec_information_cofactor_merge.py - 4 tests replicating the cognate_ligands_df concat/groupby block to verify ligand_source plumbing and the strict-addition invariant.
• Full existing test suite (6 pre-existing test files) still passes unchanged.
• Full pipeline run against real reference data (not done in this session - needs the full data_dir setup).

Known, explicitly out-of-scope gap: chlorophyll and other free-text-only UniProt COFACTOR annotations (~0.7% of the bulk pull) aren't mechanically resolvable by this path - deferred to a separate LLM-extraction follow-on per the plan doc.

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