Why I built this. I'm not just studying reverse-ageing — I'm living it. I follow reverse-ageing protocols (hormonal therapies, peptides, Bryan Johnson's Blueprint), and I track the field's clinical frontier — like David Sinclair's epigenetic-reprogramming research as it advances through FDA trials. That obsession is what pushed me to stop only reading about longevity science and start building with it. After working through the books and the papers, I wanted to probe the biology of ageing with my own hands — so I started building tools. This is one of them.
A small, reproducible structure-based drug–target docking and validation pipeline: AlphaFold2 structure prediction → binding-pocket docking (AutoDock Vina) → redocking RMSD validation.
Everything here runs on a laptop (built and tested on Apple Silicon, CPU-only) with free, open tools — no GPU and no cloud required.
It is easy to dock a molecule into a protein and get a number. It is much harder to show that number is trustworthy. The standard test is redocking: take a crystal structure with a ligand already bound, remove the ligand, dock it back, and measure how close the docked pose is to the experimental one (RMSD). Under ~2 Å is considered a successful reproduction of the experimental binding mode. This repo automates that test.
Two clinically important compounds, each redocked into its target:
| Compound | Target | Binding affinity | Redock RMSD | PDB |
|---|---|---|---|---|
| Rapamycin (sirolimus) | FKBP12 | −11.09 kcal/mol | 0.53 Å | 1FKB |
| Navitoclax (ABT-263) | Bcl-xL | −10.56 kcal/mol | 0.90 Å | 4QNQ |
Both redock RMSDs are well under the 2 Å threshold — the pipeline reproduces known binding modes, so its affinity estimates are credible.
Plus a structure-prediction sanity check — the rapamycin-binding FRB domain of mTOR folded with AlphaFold2 (LocalColabFold), mean pLDDT 92.8 (highest-confidence tier), the binding-anchor residue at pLDDT 94.
| mTOR FRB fold (pLDDT) | Rapamycin → FKBP12 | Navitoclax → Bcl-xL |
|---|---|---|
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In the docking panels, green = experimental (crystal) pose, cyan = docked pose — the near-perfect overlap is the sub-1 Å validation, visualised.
# fetch a holo structure, then redock its native ligand:
curl -O https://files.rcsb.org/download/1FKB.pdb
scripts/redock.sh 1FKB.pdb RAP A FKBP12_RAPAOutput: binding affinity (kcal/mol) and redock RMSD vs the crystal pose.
- Structure prediction: AlphaFold2 via LocalColabFold
- Docking: AutoDock Vina 1.2.x
- Cheminformatics: RDKit, Meeko, Open Babel
- Rendering: PyMOL (open source)
See SETUP.md for installation.
MIT