The role of quantum mechanics in structure-based drug design

Herein we will focus on the use of quantum mechanics (QM) in drug design (DD) to solve disparate problems from scoring protein–ligand poses to building QM QSAR models. Through the variational principle of QM we know that we can obtain a more accurate representation of molecular systems than classical models, and while this is not a matter of debate, it still has not been shown that the expense of QM approaches is offset by improved accuracy in DD applications. Objectively validating the improved applicability and performance of QM over classical-based models in DD will be the focus of research in the coming years along with research on the conformational sampling problem as it relates to protein–ligand complexes.