molclaw-rgroup-sampling

name	molclaw-rgroup-sampling
description	Generate new molecules by decorating a scaffold with R-groups at specified attachment points, using LibInvent for scaffold-constrained molecular generation.
license	MIT license
metadata	{"skill-author":"PJLab"}

R-Group Molecule Generation (LibInvent)

When to Use This Tool

Use LibInvent R-group sampling when you have a fixed molecular scaffold with defined attachment points and want to explore different substituents. Ideal for SAR studies, scaffold decoration, and library enumeration.

Do NOT use when: you want to modify the overall structure (use reinvent_mol2mol_sampling); you want RL-driven R-group optimization toward property targets (use libinvent_rgroup_optimization).

Tool 1: libinvent_rgroup_sampling_by_scaffold — Custom Scaffold

Generate molecules by decorating a user-provided scaffold at marked R-group positions.
Args:
    scaffold (str): Scaffold SMILES with R-group positions marked as [*:1], [*:2], etc. Example: 'c1ccc([*:1])cc1C(=O)N[*:2]'
    n (int): Number of molecules to sample
    lipinski (bool): Default True
    filter_preset (str): Options: 'none', 'minimal', 'default', 'strict'. Default 'default'.
Return:
    status (str): 'success' or 'error'
    msg (str): Descriptive message
    save_smiles_file (str): Path to saved CSV with decorated molecules and properties
    output_smiles_list (List[str]): List of generated fully-decorated SMILES

Tool 2: libinvent_rgroup_sampling_by_scaffold_name — Predefined Scaffolds

Generate molecules using a predefined common drug scaffold.
Args:
    scaffold_name (str): Options:
        - 'benzamide': amide-linked biaryl
        - 'biphenyl': biphenyl axis
        - 'pyrimidine': trisubstituted pyrimidine
        - 'indole': indole scaffold
        - 'quinoline': quinoline scaffold
        - 'piperidine_phenyl': phenylpiperidine
        - 'sulfonamide': sulfonamide
        - 'phenyl': disubstituted phenyl
        - 'pyridine': pyridine
        - 'morpholine': morpholine
        - 'triazine': triazine
        - 'trisubstituted_benzene': 1,3,5-trisubstituted benzene
    n (int): Number of molecules to sample
    filter_preset (str): Default 'default'
    lipinski (bool): Default True
Return:
    Same as Tool 1

Scaffold SMILES Format

Mark each R-group position with [*:N] (N = unique integer):

• 1 position: c1ccc([*:1])cc1
• 2 positions: c1ccc([*:1])cc1C(=O)N[*:2]
• 3 positions: [*:1]c1cc([*:2])nc([*:3])n1

Common mistakes: Use [*:1] not [*1] or bare *. Ensure valid RDKit-parseable SMILES.

Usage Examples

# Custom scaffold
response = await client.session.call_tool(
    "libinvent_rgroup_sampling_by_scaffold",
    arguments={"scaffold": "c1ccc([*:1])cc1C(=O)N[*:2]", "n": 100, "lipinski": True, "filter_preset": "default"}
)

# Predefined scaffold
response = await client.session.call_tool(
    "libinvent_rgroup_sampling_by_scaffold_name",
    arguments={"scaffold_name": "pyrimidine", "n": 100, "lipinski": True, "filter_preset": "default"}
)

Important Notes

1. Output is the fully decorated molecule, not the R-group fragment alone.
2. For RL-driven R-group optimization with property targets, use libinvent_rgroup_optimization instead.
3. Custom scaffold parsing errors are the most common failure. If the tool errors, try by_scaffold_name with the closest predefined scaffold as a diagnostic.

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⚠ Mandatory Generation Count Verification (L3 Principle 11)

actual_count = len(result["output_smiles_list"])

If actual count < 70% of requested: Retry with filter_preset='minimal' or increased n.