molclaw-linker-sampling

name	molclaw-linker-sampling
description	Generate linker molecules connecting two warhead fragments, for applications such as PROTAC design, bivalent ligands, and fragment merging.
license	MIT license
metadata	{"skill-author":"PJLab"}

Linker Molecule Generation (LinkInvent)

When to Use This Tool

Use LinkInvent linker sampling when you have two molecular fragments (warheads) and need to generate linker structures connecting them. Common applications include PROTAC design, bivalent ligand construction, and fragment-based drug design.

Do NOT use when: you want to modify a complete molecule (use reinvent_mol2mol_sampling); you want to add R-groups to a scaffold (use libinvent_rgroup_sampling).

Tool 1: linkinvent_linker_sampling_by_warheads — Custom Warhead SMILES

Generate linker molecules connecting two user-specified warhead fragments.
Args:
    warheads (str): SMILES of two warheads separated by '|'. Each warhead must contain exactly one '*' attachment point. Example: '*c1ccc(O)cc1|*N1CCNCC1'
    n (int): Number of molecules to sample
    filter_preset (str): Options: 'none', 'minimal', 'default', 'strict'. Default 'default'.
    lipinski (bool): Default True. Set False for PROTACs (inherently large).
    min_linker_atoms (int): Minimum heavy atoms in linker. 0 = no constraint. Default 0.
    max_linker_atoms (int): Maximum heavy atoms in linker. 0 = no constraint. Default 0.
Return:
    status (str): 'success' or 'error'
    msg (str): Descriptive message
    save_smiles_file (str): Path to saved CSV
    output_smiles_list (List[str]): List of generated linked molecule SMILES

Tool 2: linkinvent_linker_sampling_by_warhead_pair_name — Predefined Pairs

Generate linker molecules using a predefined warhead pair (no SMILES needed).
Args:
    warhead_pair_name (str): Options:
        - 'phenyl_phenyl', 'phenyl_pyridine', 'phenyl_piperidine',
        - 'phenyl_morpholine', 'pyridine_morpholine', 'phenol_furan',
        - 'indole_piperazine', 'thiophene_piperazine', 'benzamide_piperidine'
    n (int): Number of molecules to sample
    filter_preset (str): Default 'default'
    lipinski (bool): Default True
    min_linker_atoms (int): Default 0
    max_linker_atoms (int): Default 0
Return:
    Same as Tool 1

Linker Length Guide

Application	min_linker_atoms-max_linker_atoms	Rationale
Fragment merging	1-5	Short, rigid
Bivalent ligand	3-8	Moderate flexibility
PROTAC (CRBN-based)	6-12	Shorter preferred for CRBN
PROTAC (VHL-based)	8-15	Longer often needed

Usage Examples

# Custom warheads
response = await client.session.call_tool(
    "linkinvent_linker_sampling_by_warheads",
    arguments={
        "warheads": "*c1ccc(O)cc1|*N1CCNCC1",
        "n": 50, "lipinski": True, "filter_preset": "default",
        "min_linker_atoms": 3, "max_linker_atoms": 8
    }
)

# Predefined pair
response = await client.session.call_tool(
    "linkinvent_linker_sampling_by_warhead_pair_name",
    arguments={
        "warhead_pair_name": "phenyl_piperidine",
        "n": 50, "lipinski": False, "filter_preset": "default",
        "min_linker_atoms": 6, "max_linker_atoms": 12
    }
)

---

⚠ Mandatory Generation Count Verification (L3 Principle 11)

actual_count = len(result["output_smiles_list"])

If actual count < 70% of requested: Retry with looser filter_preset, wider linker atom range, or increased n.