Combinatorial efficiency

Combinatorial Hbraries are limited by the number of sequences that can be synthesized. For example, a Hbrary consisting of one molecule each of a 60-nucleotide sequence randomized at each position, would have a mass of >10 g, weU beyond the capacity for synthesis and manipulation. Thus, even if nucleotide addition is random at all the steps during synthesis of the oligonucleotide only a minority of the sequences can be present in the output from a laboratory-scale chemical DNA synthesis reaction. In analyzing these random but incomplete Hbraries, the protocol is efficient enough to allow selection of aptamers of lowest dissociation constants (K ) from the mixture after a small number of repetitive selection and amplification cycles. Once a smaller population of oligonucleotides is amplified, the aptamer sequences can be used as the basis for constmcting a less complex Hbrary for further selection. 

Chemoinformatics (or cheminformatics) deals with the storage, retrieval, and analysis of chemical and biological data. Specifically, it involves the development and application of software systems for the management of combinatorial chemical projects, rational design of chemical libraries, and analysis of the obtained chemical and biological data. The major research topics of chemoinformatics involve QSAR and diversity analysis. The researchers should address several important issues. First, chemical structures should be characterized by calculable molecular descriptors that provide quantitative representation of chemical structures. Second, special measures should be developed on the basis of these descriptors in order to quantify structural similarities between pairs of molecules. Finally, adequate computational methods should be established for the efficient sampling of the huge combinatorial structural space of chemical libraries. 

Combinatorial chemistry constitutes a branch of the molecular sciences, providing an array of concepts and methods to solve molecular optimization problems (in drug research and beyond) more rapidly and efficiently than classical synthetic approaches. 

These conceptual goals are attained by several combinatorial methods and tools. Characteristic for combinatorial chemistry is the synthesis on solid support or by polymer-supported synthesis, allowing for much higher efficiency in library production. Synthesis can be conducted either in automated parallel synthesis or by split-and-recombine synthesis. Centerpieces of combinatorial methods further include specific analytical methods for combinatorial... 

Precisely defined collections of different chemical compounds are denominated as chemical libraries that can be efficiently prepared by methods of combinatorial chemistry. Each chemical compound owes specific structural, steiic, and electronic properties that determine all possible interactions of the small molecule with a given protein or receptor. The molecule s properties are based on the steiic arrangement of functional groups, including the conformations that can be attained by a specific structure. 

Combinatorial chemistry is the branch of the molecular sciences providing concepts and methods for solving problems of molecular optimization fast and efficiently. 

FlexX An extension of the FlexX docking program which increases the efficiency of the docking of combinatorial libraries Tripos, Inc. http //www.tripos.com [32]... 

Rarey M, Lengauer T. A recnrsive algorithm for efficient combinatorial library docking perspective in drug discovery and design. Perspect Drug Discov Des 2000 20 63-81. 

Sprous DG, Lowis DR, Leonard JM, Heritage T, Burkett SN, Baker DS, Clark RD. OptiDock virtual HTS of combinatorial libraries by efficient sampling of binding modes in product space. J Comb Chem 2004 6 530-9. 

Langer T, Wolber G. Virtual combinatorial chemistry and in silica screening efficient tools for lead structure discovery Pure Appl Chem 2004 76 991-6. 

Phenolic copolymers containing fluorophores (fluoroscein and calcein) were synthesized by SBP catalysis and used as array-based metal-ion sensor. Selectivity and sensitivity for metal ions could be controlled by changing the polymer components. Combinatorial approach was made for efficient screening of specific sensing of the metals. 

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