Abstract
A new method of molecular similarity analysis was applied to the three-dimensional quantitative structure-activity relationship (3D-QSAR) of neonicotinoid insecticides such as imidacloprid and acetamiprid. Two novel indices of molecular similarity were defined as inner products of vectors representing electrostatic and steric properties of molecules in three-dimensional space, respectively. The similarity indices of 12 neonicotinoids having various structures were calculated for each pair of the molecules, and a similarity matrix of the indices was generated. The partial least squares (PLS) method was employed to analyze the correlation between the receptor-binding activity and the similarity indices. A significant QSAR model was obtained on the basis of similarity and dissimilarity of the whole series of compounds, indicating that both the similarities in steric and electrostatic properties are important for the activity. The structural requirements of the molecules for the activity were visually presented by displaying the three-dimensional grid points which contribute significantly to the activity in terms of steric and electrostatic properties.
