Binding Free Energy (delta-G)

The thermodynamic quantity (delta-G) that determines the strength of non-covalent interaction between a ligand and its target protein. More negative values indicate stronger binding. Binding free energy encompasses enthalpic contributions (hydrogen bonds, van der Waals, electrostatics) and entropic contributions (desolvation, conformational changes). Accurate prediction remains a grand challenge in computational drug design.

예시

• Free Energy Perturbation (FEP+, Schrodinger) — gold standard for relative binding free energy
• MM-PBSA/MM-GBSA — endpoint free energy methods from MD trajectories
• Typical drug-target binding: delta-G of -8 to -12 kcal/mol (nM affinity)