Computer Assisted Drug Discovery (CADD)

The role of CADD is to provide scientific insight and focus to UCB's research programmes through the application of advanced modelling, simulation and data visualisation techniques. Working together and with other departments such as Informatics, the CADD groups also form a valuable global resource for developing new technologies that can be applied across the entire drug discovery process. This includes virtual screening and fragment screening (previously mentioned).  In addition, CADD plays a key role in structure-based drug design.

Structure-based Drug Design

An accurate 3-D structure model of the protein target enables the UCB scientists to see how well the drug molecule fits into the binding site of the protein of interest.  This can then direct the changes that need to be made for the molecule to become a better drug. In some cases crystal structures are generated by UCB internally, which can give rise to this accurate 3D structural model.

Accurate 3D structural models of some protein targets are not always available or can be generated. For example, many important protein receptors reside in membrane environments and are consequently very difficult to crystallise or reliably model. In these cases, the CADD focus often shifts towards making maximum use of information about known small molecule ligands. At the simplest level, we might use 2D molecular fingerprint comparison to identify alternative ligands with similar molecular structures to those we know about. A more sophisticated approach would be to build pharmacophore models - particular 3D arrangements of molecular features hypothesised as important for binding to a particular target - and then look for novel molecules that can exhibit the same pharmacophoric patterns. Alternatively, predictive mathematical models (QSAR models) may be constructed that relate calculated molecular properties and structure to measured biological activity.