Free-energy calculations - Theoretical Biophysics Group

Free-energy perturbation calculations “Alchemical transformations”
The dual–topology paradigm avoids several complica-
tions inherent to the single-topology approach.
The problem of growing or shrinking chemical
bonds is not present here.
Decoupling electrostatic and non-electrostatic
contributions during simulations is no longer
needed.
Dual–topology also suffers from problems when λ approaches
0 or 1, which are often referred to as “end-point
catastrophes”.
At these end points, interaction of the reference, or the
target topology with its environment is extremely weak,
yet still non–zero, which in turn allows the surrounding
atoms to clash against the appearing or vanishing chemical
moieties.
Chris Chipot Free-energy calculations