Searching for Similar Molecules in a Data Set

We have seen that RDF descriptors are one-dimensional representations of the 3D structure of a molecule. A classification of molecular structures containing characteristic structural features shows how the descriptor preserves effectively the 3D structure information. For this experiment, Cartesian RDF descriptors were calculated for a mixed data set of 100 benzene derivatives and 100 cyclohexane derivatives. Each compound was assigned to one of these classes, and a Kohonen neural network was trained with these data. The task for the Kohonen network was to classify the compounds according to their Cartesian RDF descriptors. 

FIGURE 6.10 Results of the classifieation with 100 benzene derivatives (dark) and 100 cycloaliphatic compounds (light). The topological map shows a clear distinction between compounds with planar benzene ring systems and nonplanar cyclic systems (rectangular network, Cartesian RDF, 128 components). 

Obviously, a Kohonen network is able to distinguish between planar and nonpla-nar structures via their descriptors. The use of this classification is that if we present a new unclassified compound to this trained network, its central neuron would indicate whether it is a benzene or cyclohexane derivative. 

The training for such an experiment is performed within seconds on a conventional personal computer. The prediction for a new compound just takes a few milliseconds the network is able to assign thousands of structures to their proper structure type within a few seconds. A comparable substructure search with conventional algorithms would take at least several hours. The method ideally is suited for automated in analysis high-throughput screening tasks. 

However, the task just described is a quite simple one, and the question is whether a classification is still successful and accurate with other structure types. If we extend a training data set with another class of structure, a new cluster occurs. The next experiment shows this with a small set of steroids included in the training set. Parts of the neurons containing descriptors of cyclic aliphatic compound split, and the steroid descriptors appear. 

---