π-π stacking tackled with density functional theory

Through comparison with ab initio reference data, we have evaluated the performance of various density functionals for describing pi-pi interactions as a function of the geometry between two stacked benzenes or benzene analogs, between two stacked DNA bases, and between two stacked Watson-Crick pairs. Our main purpose is to find a robust and computationally efficient density functional to be used specifically and only for describing pi-pi stacking interactions in DNA and other biological molecules in the framework of our recently developed QM/QM approach QUILD. In line with previous studies, most standard density functionals recover, at best, only part of the favorable stacking interactions. An exception is the new KT1 functional, which correctly yields bound pi-stacked structures. Surprisingly, a similarly good performance is achieved with the computationally very robust and efficient local density approximation (LDA). Furthermore, we show that classical electrostatic interactions determine the shape and depth of the pi-pi stacking potential energy surface.