Peak-performance de novo binders for the E3 ubiquitin machinery.
This repository contains the computational pipeline and validation data for Design_9, a synthetically designed protein binder for the RBX1 (RING-box protein 1) subunit. RBX1 is an essential component of the SCF E3 ubiquitin ligase complex, making it a high-value target for modulating protein degradation pathways.
- Backbone Scaffolding: Generated >800 scaffolds using RFdiffusion, targeting the RBX1 interface.
- Sequence Optimization: Optimized residues for binding affinity and folding stability using ProteinMPNN.
- Molecular Dynamics Validation: Conducted a 100ns production run in GROMACS (OPLS-AA force field, TIP3P water). This is our critical "physical filter" to distinguish true binders from static AI "decoys" and characterize actual flexibility beyond pLDDT metrics.
The initial lead exhibits a robust folding funnel and persistent interface contact at the RBX1 binding site.
| Backbone Stability | Compactness | Binding Persistence |
|---|---|---|
 |
 |
 |
- Structural Stability: Backbone RMSD stabilized at ~0.2 nm over 100ns.
- Compactness: Radius of gyration (Rg) remained consistent throughout.
- Binding Interface: Hydrogen bond persistence analysis confirms a stable network.
scripts/: Core analysis and visualization pipelines.utils/: Helper scripts for format conversion and animation.config/: Simulation and design parameters (.yaml, .mdp).assets/: High-fidelity visuals (GIFs, premium plots).deploy/: Containerization and HPC orchestration.
- To reproduce simulation:
gmx mdrun -s md.tpr - To analyze results:
python scripts/analyze_apex.py --mode analyze
- Project Lead: [QntmSeer]
- Simulation Infrastructure: NVIDIA L4 GPU / GCP Spot Instances.
For professional inquiries or collaboration, please reach out via LinkedIn.