Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) is a method to estimate ligand-protein binding free energy. MM/GBSA binding free energy calculations offers the advantage of being more theoretically rigorous than empirical scoring functions used by molecular docking, and the benefit of being far less computationally expensive than relative binding free energy simulations, providing a good balance between computational speed and accuracy.
- Run MM/GBSA experiments to evaluate the binding free energy of ligands, either from single conformations or over Dynamics trajectories, in a fraction of the time and cost compared to relative binding free energy calculations
- A wide variety of different implicit solvent models are available, making MM/GBSA adaptable to your protein-ligand system of interest
- Use MM/GBSA single conformation calculations for a high-throughput assessment of ligand binding affinities within your compound series at the end of a docking experiment, prioritizing your molecule designs with more confidence
- Use MM/GBSA on Dynamics to score multiple ligand-protein complexes with an associated Dynamics trajectory for a more accurate estimate of binding free energy
References and acknowledgements
S. Genheden, U. Ryde, The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities, Expert Opin Drug Discov. 2015,10, 5
E. Wang, H. Sun, J. Wang, Z. Wang, H. Liu, J. Z. H. Zhang, and T. Hou, End-Point Binding Free Energy Calculation with MM/PBSA and MM/GBSA: Strategies and Applications in Drug Design, Chem Rev. 2019 119 (16), 9478-9508
T. Tuccinardi, What is the current value of MM/PBSA and MM/GBSA methods in drug discovery?, Expert Opin Drug Discov. 2021, 16(11), 1233–1237