Specificity rational design

Rational Mutation to Widen Substrate Specificity Rational design in modification of enzyme by point mutation has been reported. The secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus 39E... 

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. 

The voluminous experimental information about the linkage between structural variables and properties of polymers is assembled in books, notably that by van Krevelen (1990). In effect, such books encapsulate much empirical knowledge on how to formulate polymers for specific applications (Uhlherr and Theodorou 1998). What polymer modellers and simulators strive to achieve is to establish more rigorous links between structural variables and properties, to foster more rational design of polymers in future. 

Because of the unambiguous reactive sites of monomers and the high chemo-and stereoselectivity of transition-metal-catalyzed coupling reactions, polymers prepared by transition metal coupling have predictable chemical structures. Functional groups can be easily and selectively introduced at the desired position within die polymer chains. Therefore, polymers widi specific properties can be rationally designed and synthesized. 

Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA 2004 101 7618-23. 

Traditional solid-state synthesis involves the direct reaction of stoichiometric quantities of pure elements and precursors in the solid state, at relatively high temperatures (ca. 1,000 °C). Briefly, reactants are measured out in a specific ratio, ground together, pressed into a pellet, and heated in order to facilitate interdiffusion and compound formation. The products are often in powdery and multiphase form, and prolonged annealing is necessary in order to manufacture larger crystals and pure end-products. In this manner, thermodynamically stable products under the reaction conditions are obtained, while rational design of desired products is limited, as little, if any, control is possible over the formation of metastable intermediates. ... 

Figure 3.1 Overview of DNA library creation strategies. Random mutagenesis introduces mutations at positions throughout the gene sequence. Semi-rational design randomizes only the specific position(s) of interest. Gene shuffling brings existing sequence diversity from different parental DNA sequences together to form a chimeric library...

Utilization of cell-specific peptide sequences in biomaterials enables the selective adhesion of certain cell types, even in the presence of a mixture of many cell types. As mentioned earlier, REDV promotes the adhesion of endothelial cells, but not other vascular cell types (Hubbell et al., 1991). This selectivity has great potential for endothelialization of vascular devices, where the growth of an endothelial cells, but not fibroblasts or smooth muscle cells, is desired. Another peptide sequence, KRSR, has been shown to selectively promote the adhesion of osteoblasts, which is useful in the rational design of better dental and orthopedic biomaterials (Dee et al., 1998). 

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