Combinatorial chemistry, computational aspects

This chapter focuses upon selection algorithms, but it is perhaps worth mentioning that genetic algorithms, and related approaches to evolutionary computing, have been applied to several aspects of combinatorial chemistry the reader is referred to the reviews by Clark for an extensive bibliography of work in this area [67, 75],... 

Computational methods are only one aspect in the strategy for drug research and development. In the past years, experimental high-throughput screening methods have been established based on molecular test systems. In favorable cases, several thousand compounds can be tested in an assay per day. This has stimulated the development of new methods to synthesize large libraries of diverse molecules. Combinatorial chemistry [88,89] offers great promise in the discovery of new leads. In our opinion, the computer-based methods nicely comple-... 

All of these demands require comparison of molecules, and therefore computation of molecular similarity is a major task in library design. When combinatorial chemistry started to become an important tool in medicinal chemistry, library design was focused mainly on synthetic accessibility, but today, all aspects of library optimization must be taken into consideration [4—7]. 

The ability of combinatorial chemistry to generate a myriad of compounds in a very short period of time sets demands upon the analytical techniques to produce a maximum of information in a minimum of time. A prime candidate for the analysis of combinatori-ally generated compounds is electrospray ionization-mass spectrometry (ES-MS) using a quadrupole mass analyzer. In the following section we wish to examine the practical aspects of ES-MS, and exemplify these on the routine analysis of several combinatorially generated compounds and libraries. Furthermore, attention will be paid to high-through-put and computer-assisted sample evaluation. 

Computational Aspects of Library Design and Combinatorial Chemistry... 

Martin, Y.C. (2001) Diverse viewpoints on computational aspects of molecular diversity. Journal of Combinatorial Chemistry, 3, 231-250. 

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