Tc-43/Novel_NLRP3_Inhibitor_Designs

Novel NLRP3 Inhibitors — GA-II Designed Ligand–Receptor Complexes

176 computationally designed small-molecule ligands docked into the NLRP3 inflammasome sensor, each provided as a single-file protein–ligand complex in PDB format (101 unique ligand structures).

NLRP3 is the sensor of the NLRP3 inflammasome; small-molecule inhibitors that engage its NACHT module suppress inappropriate IL-1β-driven inflammation across a broad range of inflammatory and metabolic diseases.

Receptor note: coordinates correspond to the NLRP3 (NACHT-containing core) (chain A res 134–676). TODO: add the source RCSB PDB accession for the receptor template used to generate these complexes.

Dataset summary

Complex files	176 (*_cmpx.pdb)
Unique ligand SMILES	101
Receptor	NLRP3 (NACHT-containing core) (chain A res 134–676)
Generator	Technetium GA-II pocket-conditioned generative platform
Generation date	2025-08-15 – 2025-10-10
Pose scoring	AutoDock Vina

These are de novo, scaffold-constrained generative designs produced by the Technetium GA-II pocket-conditioned generative platform. Each design is docked into the target pocket and scored with AutoDock Vina; a REMARK CORE record preserves the scaffold/attachment context.

Each complex file is self-contained — receptor structure, the ligand's 3D docked pose, and a 2D↔3D atom map all travel inside the single PDB.

Property profile

Physicochemical ranges are computed with RDKit over the 101 unique ligand structures; docking energy is from the generation/docking pipeline.

Property	Range	Median
Docking energy (AutoDock Vina)	≤ -9.4 kcal/mol (down to -12.4)	—
Molecular weight	363.4 – 548.6 Da	455.6
cLogP	0.8 – 4.3	3.5
TPSA	67.4 – 113.0 Ų	93.9
Fsp3 (fraction sp³ C)	0.2 – 0.6	0.3
H-bond donors	1 – 4	2
H-bond acceptors	3 – 8	5
Rotatable bonds	2 – 8	4

File format

Each *_cmpx.pdb bundles the receptor and one docked ligand pose:

Record	Content
REMARK VINA RESULT <energy> …	AutoDock Vina docking score (kcal/mol)
REMARK CORE <smiles>	the scaffold / attachment context of the design
REMARK SMILES <smiles>	the docked ligand (2D structure)
REMARK SMILES IDX <pos> <serial> …	map of each SMILES heavy-atom position ↔ its ligand atom serial (the 2D↔3D key)
ATOM … <chain>	receptor heavy atoms
ATOM … UNL (after MODEL 1)	ligand 3D pose (residue name UNL)

Usage

import glob

def read_complex(path):
    smiles, idx = None, {}
    with open(path) as fh:
        for line in fh:
            if line.startswith("REMARK SMILES IDX"):
                toks = line.split()[3:]            # flat list of (smiles_pos, atom_serial)
                for i in range(0, len(toks), 2):
                    idx[int(toks[i])] = int(toks[i + 1])
            elif line.startswith("REMARK SMILES"):
                smiles = line.split(None, 2)[2].strip()
    return smiles, idx                              # idx[smiles_atom_position] -> ligand atom serial

for f in glob.glob("*_cmpx.pdb"):
    smi, idx = read_complex(f)
    # ligand atoms are the `ATOM ... UNL` records following `MODEL 1`

Provenance & intended use

• These are computationally generated designs and docked poses — not experimentally validated binders. No claim of activity or selectivity is made.
• Intended for machine-learning, cheminformatics, generative-model benchmarking, and docking-pose research on a well-defined target.

Citation

Generated by Technetium Therapeutics. Poses scored with AutoDock Vina.