Reliable energy ranking of molecular crystal polymorphs
In plain words
The same molecule can pack into several crystal forms with almost equal energies, and which form appears changes how a drug dissolves. Calculations still struggle to rank these forms correctly.
Precise statement
For organic molecular crystals with known polymorphs, compute relative lattice free energies at 300 K, including vibrational and thermal-expansion contributions, with errors below 0.25 kcal/mol per molecule, and predict the observed stable form. An answer is a method that ranks the experimentally known polymorphs correctly across a blind test set of at least 10 systems.
What would settle it
Blind crystal-structure-prediction tests with experimentally determined relative stabilities, judged on correct ranking and free-energy error.
Status in the literature
Unverified note
The seventh blind test of crystal structure prediction, organized by the Cambridge Crystallographic Data Centre with results published in 2024, found that leading methods usually generate the observed forms but do not reliably rank them first.