Library enumeration

Leach AR, Bradshaw J, Green DVS, Hann MM, Delany JJ III. Implementation of a system for reagent selection and library enumeration, profiling and design. / Chem Inf Comput Sci 1999 39 1161-72. 

Fig. 12. (see opposite page) The library enumeration interface (A) allows for up to three reactant files to be uploaded. This is also where the preference for how to handled reactants that map multiple times to the substructure as defined in the RXN file is set. These compounds can be rejected, reacted once, or they can be reacted at each matching site. The output of the library subset (B) can be visualized in a web page before downloading the entire library. 

Enumeration is the computational equivalent of carrying out a combinatorial synthesis. The result is a virtual library of product molecules that can then be analyzed using a library design program to select compounds of interest. Two different approaches to library enumeration have been developed fragment marking and the reaction-transform approach (14). 

Schuller, A., Hahnke, V, Schneider, G. (2007) SmiLib v2.0 a Java-based tool for rapid combinatorial library enumeration QSAR. Comb Sci 26, 407-110. 

OptiDOCK Uses the seed and grow strategy to first dock representative compounds spanning the chemical space of the library and subsequently use an optimal core for library enumeration (83)... 

Basis products (BPs) Exploits the redundancy of fragments in a combinatorial library and identifies a small subset of compounds (BPs) which represent the entire virtual library. BPs are docked, scored, and used for final library enumeration (85)... 

Computational library design process begins with reagent selections, followed by diversity analysis and virtual library enumeration, and ends with selection of a final set of molecular structures to be synthesized (Fig. 9.4). Two databases, Available Chemical Database (ACD) (2) and Chemicals Available for... 

Reagents with multiple reactive chemical groups should be avoided in library enumeration because their presence most likely requires specific protections of certain functional groups which complicates chemical reactions and makes library production unpractical. 

Click on the Enumerator tab to proceed to the library enumeration workspace. 

Fig. 18.4. Chemical library enumeration, (a) Initiation for the scaffold and block lists, (b) Illustration on the usage of the enumerator.

Service-oriented architecture (SOA) is a hot topic these days and is considered by many people to be the enterprise computing framework of the future. In SOA, each software unit runs on a piece of hardware as a service that can be called by many different consumers. For example, a compound registration service can be called by a library enumeration tool and a chemistry e-notebook to fulfill compound registration tasks. The most popular SOA is Web services that are based on HTTP and XML or SOAP standards although SOA as a concept has existed for awhile and is not limited to Web services. SOA has a lot of advantages, the most important of which is code reuse and improved productivity. However, it also presents a lot of challenges. 

Figure 7.7 Combinatorial molecule assembly scheme. Resultant candidate molecules are objects that have building-blocks attached to scaffolds via linkers. Three user-definable fragment sets are needed to feed the algorithm with fragments for each domain. A few example fragments of each type are shown for clarity. For virtual library enumeration, each database fragment gets linked to each other fragment following a combinatorial assembly scheme.

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