The use of knowledge based methods, i.e. methods that make use of experimental crystal structure information, is becoming more prevalent in both life and materials science molecular modelling. The Cambridge Structural Database (CSD) has an important role to play in the development of these tools and so this is a key area of research for the CCDC. One strand of this is the exploration of how tools and methods, created originally for use in crystal-form research, can be applied in the field of drug discovery. CCDC is in a unique position to take advantage of this cross-over technology. In addition we have active collaborative programs with a number of industrial and academic partners, aimed at developing new or improved, drug design tools. One such collaboration has resulted in a novel, highly effective superposition program for creating hypothetical pharmacophores.

Research Plans

Future research will be based around three broad areas. In one, we wish to develop methods that allow the use of CSD structures to provide good geometry fragments for the re-scaffolding of drug molecules and for linking fragments of known binding mode with geometrically acceptable linkers. The second is aimed at using all the information on molecular interactions in the CSD to validate ligand/protein interactions in modelled complexes, and hence validate the models themselves. These models may have been generated through docking or through other modelling techniques such as molecular dynamics. Thirdly, we are researching novel methods of molecular superposition and use of the resulting overlays to drive ligand-based virtual screening. Lastly we are also investigating, in collaboration, new methods for the de novo design of drug molecules that are characterised by being easily synthesizeable.