A fuzzy-set approach to functional-group comparisons based on an asymmetric similarity measure

Abstract

A new, fuzzy-set framework for molecular similarity analysis is proposed. Recent advances in the computation of ab initio quality fuzzy electron densities of molecular fragments, pharmacophoric moieties, and functional groups of both small and macromolecular systems have motivated the search for new approaches to the evaluation of molecular similarity. Fuzzy-set methods appear especially suitable for the task for two reasons: the inherent fuzziness of electron densities due to Heisenberg's quantum mechanical uncertainty relation, and the fuzzy range of possible local molecular conformations which may correlate with a given chemical or biochemical function. In this contribution, a new, asymmetric similarity measure is proposed for local molecular moieties, such as functional groups or pharmacophores, based on a fuzzy-set description of electron densities and a fuzzy-set adaptation of earlier scaling–nesting similarity measures. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 74: 503–514, 1999