Free-energy calculations - Theoretical Biophysics Group

Free-energy perturbation calculations “Alchemical transformations”
32 GAO ET AL. (1989); BORESCH, KARPLUS (1999a,b)
In contrast with the single-topology paradigm, the topologies
of the reference, 0, and the target, 1, states coexist
in the dual–topology scheme, throughout the “alchemical
transformation”. 32
Using an exclusion list, atoms that are not common to 0
and 1 never interact during the simulation.
Their intra– and intermolecular interaction with other
atoms in the system are scaled by λ, which varies from
0 to 1.
In the initial state, only topology 0 interacts with the rest
of the system, whereas in the final state, only topology 1
does:
U(x; λ) = λU1(x) + (1 − λ)U0(x)
Chris Chipot Free-energy calculations