MM/PBSA vs MM/GBSA: Which Rescoring Method Fits Your System

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

The practical difference between MM/PBSA and MM/GBSA: how PB and GB solvation models work, accuracy vs speed trade-offs, which to use for charged ligands, metal sites and congeneric series, and why consistency beats method choice.

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
• 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
• 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
• Wang, J., Wang, W., Kollman, P.A. & Case, D.A. MMPBSA.py. J. Comput. Chem. 25, 1157-1174 (2004). DOI: 10.1002/jcc.20035
• Massova, I. & Kollman, P.A. Combined molecular mechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding. Perspect. Drug Discov. Des. 18, 113-135 (2000).

Scope & Limitations

PB and GB variants differ by implementation (igb settings, dielectric constants, radii sets); conclusions here generalize across common setups but individual systems vary Both methods are end-point approximations; neither approaches alchemical FEP/TI accuracy for absolute affinities