Assessing molecular similarity from results of ab initio electronic structure calculations

A new molecular similarity index, called the number of overlapping electrons (NOEL), is proposed. This similarity index can be computed very rapidly from the natural orbitals and their occupation numbers of the molecules under comparison. The low computational cost makes it possible to optimize the mutual orientation of molecules by maximizing NOEL. The magnitude of NOEL is related to the number of electrons in the molecular fragment common to both molecules. The new approach is illustrated on the examples of benzene, aniline, nitrobenzene, and 4-nitroaniline molecules and the acetate, isoxazole 3-oxide and isoxazole 5-oxide anions.