Free-energy calculations - Theoretical Biophysics Group

Free-energy perturbation calculations Measuring the error associated to an FEP calculation
A naive view of this problem can be put forth in terms of
a frontier value of the perturbation, ∆U0, below which,
in a forward transformation, states characterized by an
energy difference ∆U < ∆U0 are never sampled.
The systematic error then arises from failure to explore
important regions of configurational space that correspond
to ∆U < ∆U0.
In the ergodic limit, the exact free-energy difference, ∆A,
of a forward transformation can be expressed as a sum
of two contributions reflecting sampling of regions above
and below the frontier value, ∆U0,
exp(−β∆A) =
+
∆U0
P0(∆U) exp(−β∆U) d∆U
−∞
+∞
P0(∆U) exp(−β∆U) d∆U
∆U 0
Chris Chipot Free-energy calculations