Tc-43/CyclinA_RXL_PPI_BLOCKER

Cyclin A RxL PPI Blockers — Ligand–Receptor Complexes

57 computationally designed small-molecule ligands docked into Cyclin A (RxL substrate groove), each provided as a single-file protein–ligand complex in PDB format (56 unique ligand structures).

These designs block the RxL / cyclin-binding-motif groove of Cyclin A, the docking site through which cyclin-CDK complexes recruit substrates — a protein–protein-interaction strategy for selective cell-cycle intervention.

Receptor note: coordinates correspond to the Cyclin A (RxL substrate-recruitment groove) (chain B res 175–432). TODO: add the source RCSB PDB accession for the receptor template used to generate these complexes.

Dataset summary

Complex files	57 (*_cmpx.pdb)
Unique ligand SMILES	56
Receptor	Cyclin A (RxL substrate-recruitment groove) (chain B res 175–432)
Generator	Technetium GA-II pocket-conditioned generative platform
Generation date	2025-08-30 – 2025-09-07
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 56 unique ligand structures; docking energy is from the generation/docking pipeline.

Property	Range	Median
Docking energy (AutoDock Vina)	≤ -9.2 kcal/mol (down to -10.6)	—
Molecular weight	424.5 – 596.8 Da	514.2
cLogP	1.5 – 5.0	3.8
TPSA	51.6 – 110.9 Ų	95.1
Fsp3 (fraction sp³ C)	0.2 – 0.5	0.4
H-bond donors	1 – 4	2
H-bond acceptors	5 – 9	7
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.