Pi stacking is prevalent in protein crystal structures and also contributes to the interactions between small molecules and proteins
As a result, pi–pi and cation–pi interactions are important factors in rational drug design.
Babine RE, Bender SL (August 1997). “Molecular Recognition of Proteinminus signLigand Complexes: Applications to Drug Design”. Chemical Reviews. 97 (5): 1359–1472. doi:10.1021/cr960370z. PMID11851455.
Crystal structure of Tacrine bound to acetylcholinesterase (PDB accession: 1ACJ) visualized using USCF Chimera. A pi stacking interaction between Tacrine (blue) and Trp84 (red) is proposed.
One example is the FDA-approved acetylcholinesterase (AChE) inhibitor tacrine which is used in the treatment of Alzheimer’s disease. Tacrine is proposed to have a pi stacking interaction with the indolic ring of Trp84, and this interaction has been exploited in the rational design of novel AChE inhibitors.
da Silva CH, Campo VL, Carvalho I, Taft CA (October 2006). “Molecular modeling, docking and ADMET studies applied to the design of a novel hybrid for treatment of Alzheimer’s disease”. Journal of Molecular Graphics & Modelling. 25 (2): 169–175. doi:10.1016/j.jmgm.2005.12.002. PMID16413803.
