KarmaDock Virtual Screening

Note:

• Local files are not directly accessible by the server. Please upload them to the server using molclaw-file-transfer before execution.
• For PDB file inputs, it is recommended to preprocess them using molclaw-pdbfixer before execution.
• Please refer to skill molclaw-scp-server to complete tool invocation.

Usage

1. KarmaDock Virtual Screening

The description of tool karmadock_tool.

Performs protein-ligand virtual screening with KarmaDock for batch ranking and optional pose export workflows.
Args:
    ligand_smi (str): Ligand SMILES input file path, required.
    protein_file (str): Protein PDB file path, required.
    crystal_ligand_file (str): Crystal ligand MOL2 file for pocket localization, required.
    score_threshold (float): Score threshold used for pose export mask, default 70.0.
    batch_size (int): Inference batch size, default 64.
    random_seed (int): Random seed for reproducibility, default 2020.
    dry_run (bool): Validate inputs and create tracked output directory without execution, default False.
Return:
    status (str): success, partial_success, or error execution status.
    msg (str): Human-readable execution summary.
    output_dir (str): Run-specific directory under tool_result/karmadock_tool_result.
    ligand_smi (str): Resolved ligand SMILES file absolute path.
    protein_file (str): Resolved protein PDB file absolute path.
    crystal_ligand_file (str): Resolved crystal ligand MOL2 absolute path.
    score_threshold (float): Effective score threshold used in this run.
    batch_size (int): Effective batch size used.
    random_seed (int): Effective random seed used.
    out_init (bool): Always True in wrapper.
    out_uncorrected (bool): Always True in wrapper.
    out_corrected (bool): Always True in wrapper.
    dry_run (bool): Effective dry-run flag.
    return_code (int | None): Delegated process return code.
    pose_export_hint (str | None): Diagnostic message when SDF export is requested but missing.
    key_files (dict): Key output files including score_csv and pose_sdf_files.
    metrics (dict): Summary metrics including num_ligands_scored and karma score extrema.

Scoring Interpretation (KarmaDock)

• score.csv columns:
  • pdb_id: ligand identifier from input library (or dataset complex ID).
  • karma_score: direct KarmaDock score from the MDN-based scoring head.
  • karma_score_ff: score after MMFF94 force-field corrected pose.
  • karma_score_aligned: score after RDKit-aligned corrected pose.
• Direction: all KarmaDock scores are interpreted as higher-is-better in ranking workflows.
• Practical readout:
  • Prefer candidates with consistently high values across karma_score, karma_score_ff, and karma_score_aligned.
  • If karma_score is high but corrected scores drop strongly, pose stability/reliability is weaker and should be down-weighted.
• Threshold usage:
  • score_threshold is a practical filtering knob and should be tuned per target/library distribution.
  • Common practice is to rank by score and select top N or top N%, instead of relying on one fixed threshold.
• Limitation note:
  • KarmaDock is efficient for large-scale prescreening, but pose physical validity can still require downstream docking/MD validation.

How to use tool karmadock_tool :

response = await client.session.call_tool(
    "karmadock_tool",
    arguments={
        "ligand_smi": "/path/to/ligands.smi",
        "protein_file": "/path/to/protein.pdb",
        "crystal_ligand_file": "/path/to/crystal_ligand.mol2",
        "score_threshold": 70.0,
        "batch_size": 64
    }
)
result = client.parse_result(response)
key_output = result["output_dir"]

Example parameter sets

# 1) Main mode: dry run check
{
    "ligand_smi": "/path/to/ligands.smi",
    "protein_file": "/path/to/protein.pdb",
    "crystal_ligand_file": "/path/to/crystal_ligand.mol2",
    "score_threshold": 70.0,
    "batch_size": 64,
    "random_seed": 2020,
    "dry_run": True
}

# 2) Variant mode: real run with stricter threshold
{
    "ligand_smi": "/path/to/ligands.smi",
    "protein_file": "/path/to/protein.pdb",
    "crystal_ligand_file": "/path/to/crystal_ligand.mol2",
    "score_threshold": 50.0,
    "batch_size": 64,
    "random_seed": 2023,
    "dry_run": False
}