Chemical mutation approach

The success of the chemical mutation approach described above depends on the ability to transform the energy function, U, from one state to another during the MD simulations. This may not be applicable if the two states are very different, or for a QM... 

The design of supramolecular catalysts may make use of biological materials and processes for tailoring appropriate recognition sites and achieving high rates and selectivities of reactions. Modified enzymes obtained by chemical mutation [5.70] or by protein engineering [5.71] represent biochemical approaches to artificial catalysts. 

Fig. 1. Comparison of genetic and chemical genetics. In the traditional genetics approach genes are mutated resulting in missing or altered protein products. In a chemical genetic approach, compounds bind to specific proteins modulating their normal physiological functions. The throughput at steps A, B, C is used in Table 1 to help define the different chemical genetic approaches.

Bora, K. C. 1976. A hierarchical approach to mutagenicty testing and regulatory control of environmental chemicals. Mutat. Res. 46 145. 

The final example of our chemical genetic approach to dissect herbicide action involves auxin biology. A subset of our bioactive compound library that exhibited auxinic herbicidal symptoms was tested for inhibition of root growth of Arabidopsis seedlings. The most potent of these compounds was a novel picolinate auxin DAS534. Previous mutational studies with 2,4-D have elucidated an auxin signal-... 

The chemical genetic approach allowed the interplay between proteins (ShhN, Patched and Smoothened) to be studied using a pair of small molecule tools (robotnikinin and purmorphamine). The study complemented previous work which demonstrated that cyclopamine - a natural product that antagonises Smoothened - could reverse the effects of mutations in Patched. In both cases, the effects of modulating Patched - either indirectly, by targeting ShhN with Robotnikinin, or by mutation - could be reversed by antagonising Smoothened. 

Unlike rapamycin, the majority of kinase inhibitors are ATP competitive, thus making die dissection of dieir effects more difficult because of off-target effects. The first rqiorted Akt inhibitor, A-443654, is a case in point. We thus turned to a chemical genetic approach to develop highly selective Akt inhibitors. Mutation of the... 

Grant WF (1994) The present status of higher plant bioassays for the detection of environmental mutagens. Mutat Res 310 175-185 Grant WF, Owens ET (2001) Chromosome aberrations in Pisum for the study of environmental mutagens. Mutat Res 488 93-118 Kalweit S, Utesch D, von der Hude W, Madle S (1999) Chemically induced micronucleus formation in V79 cells-comparison of three different test approaches. Mutat Res 439 183-190... 

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