Free-energy calculations - Theoretical Biophysics Group

protein + ligand
0
∆ Aannihilation
protein + nothing
∆ Abinding
∆ A =0
∆ Arestrain
Free-energy perturbation calculations “Alchemical transformations”
protein ... ligand
1
∆ Aannihilation
protein ... nothing
Alternative route: Double annihilation of the ligand,
∆Abinding = ∆A 0 annihilation − ∆A1 annihilation
This implies obtaining ∆A0 annihilation and ∆A1 annihilation in the
thermodynamic cycle.
FEP is the appropriate technique, which, however, some
care.
Chris Chipot Free-energy calculations