  Methods to efficiently determine the relative stability of polymorphs of
organic crystals are highly desired in crystal structure predictions (CSPs).
Current methodologies include use of static lattice phonons, quasi-harmonic
approximation (QHA), and computing the full thermodynamic cycle using replica
exchange molecular dynamics (REMD). We found that 13 out of the 29 systems
minimized from experiment restructured to a lower energy minima when heated
using REMD, a phenomena that QHA cannot capture. Here, we present a series of
methods that are intermediate in accuracy and expense between QHA and computing
the full thermodynamic cycle which can save 42-80% of the computational cost
and introduces, on this benchmark, a relatively small (0.16 +/- 0.04 kcal/mol)
error relative to the full pseudosupercritical path approach. In particular, a
method that Boltzmann weights the harmonic free energy of the trajectory of an
REMD replica appears to be an appropriate intermediate between QHA and full
thermodynamic cycle using MD when screening crystal polymorph stability.
