(606b) Identifying and Addressing the Weaknesses of Density Functional Theory for Crystal Structure Prediction

Density functional theory has enabled major advances in pharmaceutical crystal structure prediction. Despite these successes, however, there are challenges. Delocalization error inherent in the approximate functionals can bias crystal structure predictions toward certain types of structures. We have found quite a few examples of this problematic behavior in describing the intramolecular conformational energies, for example. Descriptions of the intermolecular interactions in the lattice can also be problematic. Examples of these issues and strategies for addressing them will be discussed.