Real-time neuromorphic spike detection of druggable pockets at the MYC–MAX protein–protein interface. Sub-5-minute discovery on consumer GPU hardware.
PRISM-4D neuromorphic spike detection identified one druggable site at the MYC–MAX PPI interface
PDB: 1NKP docked with 10058-F4 (Cyan)
UniDock GPU → GNINA CNN rescore → MM-GBSA binding free energy
Contacts: A:GLU60, A:SER56 (Salt Bridge)
Contacts (3): Hydrophobic: A:TYR53 (3.61Å), A:ALA52 (3.48Å), A:LEU55 (3.67Å)
Contacts (3): Hydrophobic: A:ALA52 (3.52Å), A:LEU55 (3.71Å), A:LEU59 (3.89Å)
RDKit-derived physicochemical properties, Lipinski Ro5, ESOL solubility, QED
| Ligand | MW | cLogP | HBA | HBD | TPSA | RotB | QED | Lipinski | Veber | Solubility | BBB | CYP | PAINS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MYCi975 | 408.5 | 5.1 | 4 | 2 | 52.4 | 5 | 0.21 | FAIL | PASS | Insoluble | Possible | High | 1 |
| 10058-F4 | 230.3 | 4.24 | 2 | 1 | 20.2 | 2 | 0.82 | PASS | PASS | Moderately soluble | Unlikely | High | 0 |
| KJ-Pyr-9 | 371.5 | 4.08 | 3 | 0 | 36.4 | 2 | 0.68 | PASS | PASS | Moderately soluble | Unlikely | High | 0 |
UV pump-probe + LIF neuromorphic + EFP polar detection → 3D pharmacophore features
25 residues within 8Å of centroid across both chains
| Chain | Residue | ID | Distance (Å) | Atoms | Catalytic |
|---|---|---|---|---|---|
| B | ILE | 137 | 0.76 | 19 | |
| A | VAL | 57 | 2.36 | 16 | |
| A | ILE | 54 | 2.95 | 19 | |
| A | TYR | 53 | 3.43 | 21 | |
| A | ALA | 52 | 3.48 | 6 | |
| A | LEU | 55 | 3.67 | 8 | |
| B | TYR | 136 | 3.86 | 20 | |
| B | GLU | 135 | 4.20 | 3 | CATALYTIC |
| A | SER | 56 | 6.56 | 7 | CATALYTIC |
| A | GLU | 60 | 6.95 | 4 | CATALYTIC |
Fragment placement hotspots derived from spike-based pharmacophore analysis
| Priority | Type | Position | Recommendation | Detection |
|---|---|---|---|---|
| HIGH | BNZ | (61.7, 67.1, 37.9) | Place aryl, halogenated aryl, fused aromatics | 258nm PHE excitation |
| HIGH | BNZ | (66.7, 61.0, 42.2) | Place aryl, halogenated aryl, fused aromatics | 258nm PHE excitation |
| MED | UNK | (62.8, 60.0, 37.4) | PEG linker, alkyl chain, macrocyclic constraint | LIF neuromorphic |
Computational pipeline and literature citations
| Binding Detection | PRISM-4D GPU neuromorphic spike detection (UV pump-probe 258/274nm + LIF thermal + EFP electrostatic) |
| Simulation | 10 independent CUDA streams, 35,000 steps each, AMBER ff14SB, OptiX ray-traced solvent |
| Docking | UniDock v1.1.3 (GPU Vina) → GNINA v1.3.2 CNN rescore (dense_1_3 ensemble) |