E-STATE FIELDS - APPLICATIONS TO 3D QSAR

The derivation of a new 3D QSAR field based on the electrotopological state (E-state) formalism is described. A complementary index and its associated field, the HE-stale, describing the polarity of hydrogens i s also defined. These new fields are constructed from a nonempirical i ndex that incorporates electronegativity, the inductive influence of n eighboring atoms, and the topological state into a single atomistic de scriptor. The classic CoMFA steroid test data set was examined with mo dels incorporating the E-state and HE-state fields alone and in combin ation with steric, electrostatic and hydropathic fields. The single be st model was the E-state/HE-state combination with q(2)=0.803 (three c omponents) and r(2)=0.979. Using the E-state and/or HE-state fields wi th other fields consistently produced models with improved statistics, where the E-state fields provided a significant, if not dominant, con tribution.