Benefits of hybrid QM/MM over traditional classical mechanics in pharmaceutical systems.

• This review highlights the role of the hybrid quantum mechanics/molecular mechanics (QM/MM) technique in the drug design process. • It discusses the methodological considerations necessary to increase accuracy and to reduce the number of false-positive results. • It lists examples of various pharmaceutical systems recently studied in this context. • It provides an outlook on different successful and challenging aspects of drug design concerning the hybrid approach. Hybrid quantum mechanics/molecular mechanics (QM/MM) is one of the most reliable approaches for accurately modeling and studying the complex pharmaceutical discovery system. Classical mechanics has significantly accelerated the drug discovery process in the past decade. However, the current challenge is the large pool of false positives, which require extensive validation. Hybrid QM/MM is an effective solution for accurately studying ligand binding, structural mechanisms, free energy evaluation, and spectroscopic characterization. This article highlights the methodological details relevant to cost-effective hybrid QM/MM methods. This approach, combined with traditional pharmacoinformatics methods, could be a reliable strategy to balance the cost and accuracy of the calculations. [ABSTRACT FROM AUTHOR]