Free-energy calculations - Theoretical Biophysics Group

16 PEARLMAN, KOLLMAN (1989)
Free-energy perturbation calculations How to deal with large perturbations?
17 KULLBACK, LEIBER (1951); POHORILLE ET AL. (2010)
As a function of the problem of interest, choosing intermediate
states separated by a constant ∆λ may not be
the best possible choice — e.g. charging of a Lennard–
Jones particle, for which ∆A is a quadratic function of the
charge.
How should N and ∆λi be chosen?
One method for optimizing both N and ∆λi consists in
starting with short runs with a large N and select the
number of intermediate states and the corresponding values
of the coupling parameter on the basis of these runs,
such that the estimated variances in P(∆Ui,i+1) are sufficiently
small and approximately equal. 16
N and ∆A are related through the work dissipated in the
process: 17 N0 ∝ exp(βW1) and N1 ∝ exp(βW0), where
W0 = 〈∆U〉0 − ∆A and W1 = −〈∆U〉1 + ∆A.
Chris Chipot Free-energy calculations