  We describe a method that focuses sampling effort on a user-defined selection
of a large system, which can lead to substantial decreases in computational
effort by speeding up the calculation of nonbonded interactions. A naive
approach can lead to incorrect sampling if the selection depends on the
configuration in a way that is not accounted for. We avoid this pitfall by
introducing appropriate auxiliary variables. This results in an implementation
that is closely related to configurational freezing and elastic barrier
dynamical freezing. We implement the method and validate that it can be used to
supplement conventional molecular dynamics in free energy calculations
(absolute hydration and relative binding).
