Syllabus
1. Pioneers of free energy calculations (1935 Kirkwood, 1938 Landau, 1954 Zwanzig, 1963 Widom, 1967 McDonald & Singer, 1984 McCammon, 1985 Jorgensen)
2. Examples of the use of free energy calculations (solvation free energy, comparison of the binding abilities of inhibitors to the active site of the enzyme, the effect of point mutations of amino acids on ligand binding, energy barrier during drug passage through the cell membrane)
3. Methods based on histograms and probability distributions
4. Calculations of free energy differences through perturbation theory
5. Thermodynamic integration
6. Alchemical calculations of free energy, thermodynamic cycles
7. Calculations of relative binding free energy
8. Calculations of absolute binding free energy
9. Free energy profile calculations
10. Umbrella Sampling Methods, Blue Moon, Adaptive Biasing Force, Metadynamics
11. Non-equilibrium methods for calculating equilibrium free energy
12. Free energy calculations as a tool for rational drug design
Annotation
Protein-ligand binding and drug partitioning across the cell membrane, which are of paramount importance in the field of computer-aided, rational drug design, cannot be predicted reliably without the knowledge of the associated free energy changes. These lessons and practical exercises provide a systematic review of the methods that can be used for free energy calculations.