Free-energy calculations - Theoretical Biophysics Group

Free-energy perturbation calculations “Alchemical transformations”
1 Build the topologies representative of state 0 and state 1, and establish an exclusion
list to prevent atoms that are not common to 0 and 1 from interacting.
2 Generate an ensemble of configurations that are representative of the reference
state, λ.
3 For each configuration, evaluate the potential energy using the reference state
Hamiltonian, U(x; λ).
4 Repeat the same calculations using the Hamiltonian of the target state.
5 For each configuration, evaluate the potential energy difference.
6 Compute the ensemble average 〈exp {−β [U(x; λ + ∆λ) − U(x; λ)]}〉 λ , from
which the free energy difference ∆A = A(λ + δλ) − A(λ) can be derived.
7 Increment λ and go to stage 2.
Chris Chipot Free-energy calculations