Protein-Protein Interaction (PPI) Predictions on the Protein P48047
Joris Stroo and Mai Nguyen
Course: Bioinformatica, Bsc. Biologie
29 May 2026
Peripheral stalk and stator of the ATP synthase complex
- Connects the catalytic head to the membrane sector
- Mechanical stability
Adapted from Lai et al. (2023)
Data
Bait protein: P48047
Project goal
Track C: 12 proteins
Project Goal
Find plausible direct and indirect interactions between P48047 and other proteins within the given set of proteins, based on AlphaFold3 confidence metrics (pLDDT, PAE), visual inspection and binding energies.
Workflow
| Step | Description | Goal |
|---|---|---|
| 1 | Inspect starting pair | Get an impression of prediction reliability |
| 2 | Inspect comparison pair | Get an impression of prediction reliability |
| 3 | Construct interaction network | Find indirect interactions |
| 4 | Literature search on indirect interactions | Verify prediction network |
AlphaFold: starting pair
P48047 X Q5QNZ2
Starting pair: bonds
Starting pair - Confidence metrics
Global ipTM: 0.3
Global pTM: 0.4
Ranking score: 0.6
Prodigy \(\Delta G=\) -7.9 kcal/mol
AlphaFold: comparison pair
P48047 X O96008 (Mitochondrial import receptor subunit)
Comparison pair: bonds
Comparison pair: bonds
Global ipTM: 0.19
Global pTM: 0.45
Ranking score: 0.34
Prodigy \(\Delta G=\) -11.1 kcal/mol
Pairwise predicted direct interactions
| Pair | ipTM | pTM | Binding energy | Interface pLDDT | Between chain PAE |
|---|---|---|---|---|---|
| Starting pair | 0.3 | 0.4 | -7.9 | medium | mixed |
| Comparison pair | 0.19 | 0.45 | -11.1 | low | high |
Prodigy-based interaction network
Prodigy-based interaction network: Filtered
Only interactions weaker than the comparison pair (>-11.07 kcal/mol) and stronger than -6 kcal/mol
Predicted interactions with P48047
| Protein indicator | Binding energy | ATP synthase? | Mitochondrial? | Uniprot description (Bateman et al. (2024)) |
|---|---|---|---|---|
| Q5QNZ2 (starting) | -7.93 | Y | Y | ATP synthase subunit b |
| P10809 | -6.32 | N | Y | 60 kDa heat shock protein |
| P21796 | -6.47 | N | Y | Non-selective voltage-gated ion channel |
| Q15388 | -6.79 | N | Y | Mitochondrial import receptor subunit |
| P38646 | -7.81 | N | Y | Mitochondrial chaperone |
| P68871 | -8.69 | N | N | Hemoglobin subunit beta |
| P25705 | -10.12 | Y | Y | ATP synthase F(1) complex subunit alpha |
Concluding remarks
- AlphaFold3: a useful starting point for exploring possible interaction partners of P48047.
- By combining pLDDT, PAE, Binding energy, structural inspection, and experimental reports, we could distinguish plausible from unlikely interactions.
Thanks for your attention!
Questions?
References
Bateman, Alex and, Maria-Jesus Martin, Sandra Orchard, Michele Magrane, Aduragbemi Adesina, Shadab Ahmad, Emily H Bowler-Barnett, et al. 2024. “UniProt: The Universal Protein Knowledgebase in 2025.” Nucleic Acids Research 53 (D1): D609–17. https://doi.org/10.1093/nar/gkae1010.
Fleming, Jennifer, Paulyna Magana, Sreenath Nair, Maxim Tsenkov, Damian Bertoni, Ivanna Pidruchna, Marcelo Querino Lima Afonso, et al. 2025. “AlphaFold Protein Structure Database and 3D-Beacons: New Data and Capabilities.” Journal of Molecular Biology 437 (15): 168967. https://doi.org/10.1016/j.jmb.2025.168967.
Jumper, John, Richard Evans, Alexander Pritzel, Tim Green, Michael Figurnov, Olaf Ronneberger, Kathryn Tunyasuvunakool, et al. 2021. “Highly Accurate Protein Structure Prediction with AlphaFold.” Nature 596 (7873): 583–89. https://doi.org/10.1038/s41586-021-03819-2.
Lai, Yuezheng, Yuying Zhang, Shan Zhou, Jinxu Xu, Zhanqiang Du, Ziyan Feng, Long Yu, et al. 2023. “Structure of the Human ATP Synthase.” Molecular Cell 83 (12): 2137–2147.e4. https://doi.org/10.1016/j.molcel.2023.04.029.
Zhang, Yuying, Yuezheng Lai, Shan Zhou, Ting Ran, Yue Zhang, Ziqing Zhao, Ziyan Feng, et al. 2024. “Inhibition of m. Tuberculosis and Human ATP Synthase by BDQ and TBAJ-587.” Nature 631 (8020): 409–14. https://doi.org/10.1038/s41586-024-07605-8.
