MM/GBSA Rescoring: Why Your Docking Ranking Is Wrong Without It

By BioDockify Computational Research Team · October 11, 2026 · Tutorials

MM/GBSA explained from zero: what it adds over docking scores, the energy terms, entropy trade-offs, how to run it on docked poses, when it flips rankings, and honest accuracy expectations - with a worked rescoring example.

Read the complete article with tables, code and references on BioDockify.

Key References

• Hou, T., Wang, J., Li, Y. & Wang, W. Assessing the performance of the MM/PBSA and MM/GBSA methods. WIREs Comput. Mol. Sci. 1, e85 (2011). DOI: 10.1002/wcms.95
• Wang, E., Sun, H., Wang, J. et al. End-point binding free energy calculation with MM/PBSA and MM/GBSA. J. Chem. Inf. Model. 59, 936-947 (2019). DOI: 10.1021/acs.jcim.8b00753
• Genheden, S. & Ryde, U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin. Drug Discov. 10, 449-461 (2015). DOI: 10.1517/17460441.2015.1032936
• Trott, O. & Olson, A.J. AutoDock Vina. J. Comput. Chem. 31, 445-461 (2010). DOI: 10.1002/jcc.21334
• Wang, J., Wang, W., Kollman, P.A. & Case, D.A. MMPBSA.py. J. Comput. Chem. 25, 1157-1174 (2004). DOI: 10.1002/jcc.20035

Scope & Limitations

End-point methods approximate, not replace, alchemical free-energy calculations (FEP/TI); expect rank improvements, not absolute accuracy GB solvation underperforms PB for highly charged systems; MM/GBSA is weakest where induced fit or explicit water networks dominate binding