Quantum similarity of isosteres coordinate versus momentum space and influence of alignment

Molecular quantum similarity was studied for a set of peptide isosteres analyzed before by Boon et al. (Chem. Phys. Lett., 1998, 295 122). Overlap and Coulomb similarity measures in coordinate space were calculated using the TGSA (Topo-Geometrical Superposition Algorithm) algorithm for the alignment of molecules instead of the one used in the previous work, and a comparison between the superposition methods was made. Overlap and first order moment similarity indices in momentum space are computed for the same alignment. The results illustrate the importance of the alignment algorithm for the evaluation of molecular similarity in a given set of molecules and show that the degree of similarity depends dramatically on the similarity measure used and the space in which the similarity is computed. For a small set of propane derivatives where the similarity ranking is known from drug design, only momentum space similarity integrals give the expected similarity ordering.