MM/PBSA with AMBER: Tutorial, Theory, and a Free Online Alternative

By BioDockify Computational Research Team · September 19, 2026 · Tutorial

AMBER MM/PBSA tutorial: binding free energy from MD trajectories explained — the MMPBSA.py workflow, enthalpy vs entropy terms, when MM/GBSA suffices, free online calculation.

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

Key References

• Miller, B.R. et al. MMPBSA.py. J. Chem. Theory Comput. 8, 3314–3321 (2012). DOI: 10.1021/ct300418h
• Kollman, P.A. et al. Calculating structures and free energies. Acc. Chem. Res. 33, 889–897 (2000). DOI: 10.1021/ar000033j
• 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, C. et al. End-point free energy calculation with MM/PBSA and MM/GBSA. J. Chem. Inf. Model. 59, 936–949 (2019). DOI: 10.1021/acs.jcim.8b00530

Scope & Limitations

End-point methods approximate: no explicit conformational entropy unless quasi-harmonic/interaction-entropy is added Rank compounds, not absolute affinities — errors of several kcal/mol vs experiment are routine Same binding mode required; cross-mode comparison is invalid