On the importance of topological descriptors in understanding structure-property relationships

It has been generally observed in our work that molecular descriptors derived from a molecular graph theory or topological representation of structure play an important and often key role in many QSAR and QSPR models we have developed. These descriptors do not only provide the means to generate a good fit to the observed data used to train the models, but they also provide information that is needed to generate a clear physical interpretation of the underlying structure-activity or property relationships. In addition, these descriptors provide a conformation-independent method of measuring the key features of molecular structure that affect the observed properties of the molecules. These characteristics are exemplified in a model developed to predict critical micelle concentration (CMC). A model is described that exhibits excellent predictive strength, is independent of conformation of the structures used, and that yields a great deal of detail regarding the underlying structure-property relationship driving the observed CMC.