Free-energy calculations - Theoretical Biophysics Group

Free-energy perturbation calculations “Alchemical transformations”
The resulting numerical instabilities cause large fluctuations
in the estimated 〈∆U〉, attenuated only after extensive
sampling.
The most trivial one consists in splitting the reaction pathway
into windows of uneven widths, δλ, and using a large
number of narrow windows when λ approaches 0 or 1.
Equivalent to adopting a non-linear dependence of the
interaction potential energy on λ.
Clashes between the appearing atoms and the rest of the
system occur even for windows as narrow as δλ 10 −5 .
Chris Chipot Free-energy calculations