The calculation of molecular similarity: alternative formulas, data manipulation and graphical display

The use of electrostatic potential comparisons between molecules for the elucidation of structure activity relationships is now a well-established modeling technique. The Carbo and Hodgkin similarity indices are used extensively to make quantitative comparisons of this nature; yet their roots are found in the overlap of electron density distribution, with both formulas utilizing a product-based numerator. Two new similarity indices are suggested that calculate the electrostatic potential similarity using a difference-based numerator. The form of the new indices allows the creation of additional software functions that enhance the flexibility of similarity calculations and permit the creation of similarity maps. The general properties of these software functions and all indices are discussed and applied to a series of dopamine D2 receptor agonists.