Crystal structure prediction (CSP) has become a powerful tool in the pharmaceutical industry to assess the crystal form landscape of drug molecules, and to assess the risk of polymorph discovery in formulation. Despite many successes in CSP, crystal structures of some small molecules remain challenging due to high strain of the conformer and poor accuracy of quantum methods for ranking relative stability of polymorphs. Usually, molecules in the crystalline state adopt low-strain conformers with a strain energy of &lt;=3 kcal/mol. However, there is a small fraction of drug-like molecules which crystalize with higher torsional strain energy due to steric hinderance and intramolecular hydrogen bonding. On the other hand, DFT functionals that accurately rank many small molecule crystal structures, can perform poorly in some cases due to poor intramolecular conformational energies. The present study examines a few such challenging cases to demonstrate conformational preference and energetics of these drug-like molecules using dimer-expansion approach and possible ways to overcome through these challenges.

Crystal structure prediction: A few case studies on drug-like molecules

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.