A Structural Similarity Evaluation by SimScore in a Teratogenicity Information Sharing System

Many efforts have been devoted to the development of computer-aided prediction of drug toxicity over the decades, but at present, systems and programs available for predicting teratogenicity from chemical structures do not always give satisfactory answers yet, mainly because of the complex and unknown mechanism of reproductive and developmental toxicity. We developed a novel algorithm and implemented in the program “SimScore ” to evaluate quantitatively the structural similarity score of a target compound with the teratogenic drugs which are defined as serious human teratogens by the United States Food and Drug Administration. In SimScore, a molecular structure is divided into its skeletal and substituent parts in order to perform similarity comparison for these parts independently. This idea is based on that compounds with the same or similar skeleton show a similar biological activity, but their activity strengths depend on the variation of substituents. We demonstrated the usefulness of SimScore by applying it to an example. SimScore will be used in our web-based information system about teratogenicity to predict the potential risk of query compounds