To illustrate how the magnitude of the dispersion interaction generally increases with molecular size, Fig. shows two examples relevant to drug discovery, namely, a DNA intercalation ligand (the anti-tumor agent ellipticine) and also the protease inhibitor indinavir, bound in a model of the HIV protease binding site. These two systems have become standard benchmarks for noncovalent quantum chemistry. In both cases, the XSAPT + MBD interaction energy lies rather close to a benchmark CCSD(T)/CBS value. The interesting observation in the present context is the magnitude of the dispersion energy. For the DNA intercalation complex, which is an obvious example of π-stacking where dispersion might be expected to play a prominent role, the XSAPT + MBD dispersion energy is -71 kcal/mol. Meanwhile the HIVindinavir system has no obvious π-π interactions, yet the dispersion contribution is nearly twice as large, at -135 kcal/mol. In these examples, the model system for HIV-indinavir contains 323 atoms as compared to 157 atoms for the DNA-ellipticine model, and the dispersion energy is much larger in the larger model system.