Scaffold-based chemical space exploration

The chemical space exploration is an in-silico lead discovery process which is not restricted by the existing compound libraries. On the other hand, the vastness of the chemical space can pose a limit on its application. That is also the case of a recently introduced molecular morphing-based method called Molpher which is focused on exploring the space between a pair of molecules by finding a connecting path between them. However, identification of this path is, in some cases, beyond the limits of the method due to the size of the space. Therefore, we are introducing a modified approach which utilizes chemical scaffolds in the exploration process. The new approach first simplifies the start and target compounds using their scaffolds, and subsequently finds a path within a much smaller space of scaffolds. This path forms a set of guides to be used for finding a path in the original chemical space. This way the originally complex problem is broken down into smaller problems which can be solved faster. Our method shows a significant speed-up over the existing approach (about 58%) and results in an increased number of cases in which the path is found for distant molecules.