Computer representation and manipulation of combinatorial libraries

Though combinatorial libraries can be represented by enumerating the members of the library and using any of the commonly used computer representations for specific chemical structures, more compact forms are required for the processing of large ‘virtual’ libraries. Such representations can be divided into those which involve some form of ‘Markush’ or generic structure and those which use an approach based on generic reaction descriptions and sets of specific precursor molecules. This review discusses the nature of Markush structure representations, and the ways in which they are used in chemical patent information systems, and describes a number of different Markush-type representations developed especially for combinatorial libraries. Systems which utilise reaction-based library descriptions are also described, and the advantages and disadvantages of the two approaches, and the possibility of automatic interconversion between them, are discussed, along with the potential for their use in rapid analysis of library diversity.