Molecular Point Mutations

Over several decades, bacterial mutagenicity assays have played a major role as model test systems in the preliminary assessment 

Another assay which indirectly measures DNA damage (or halting of the replication fork) is the induction of prophage in the Microscreen assay this eventually measures the ability of an agent to induce the SOS system in E. coli. Reversion assays depend on mutations of a specific type at specific sites in the DNA, and require different tester strains for each type of reversion. 

Bacteria Prophage Induction other insects In-vitro In-vivo In-vitro In-vivo 

The mutagenicity of metal compounds in mammalian cells has formerly been assessed using mainly two systems  

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How can we apply molecular dynamics simulations practically. This section gives a brief outline of a typical MD scenario. Imagine that you are interested in the response of a protein to changes in the amino add sequence, i.e., to point mutations. In this case, it is appropriate to divide the analysis into a static and a dynamic part. What we need first is a reference system, because it is advisable to base the interpretation of the calculated data on changes compared with other simulations. By taking this relative point of view, one hopes that possible errors introduced due to the assumptions and simplifications within the potential energy function may cancel out. All kinds of simulations, analyses, etc., should always be carried out for the reference and the model systems, applying the same simulation protocols. 

A protein with the innocuous name p53 is one of the most frequently cited biological molecules in the Science Citation Index. The "p" in p53 stands for protein and "53" indicates a molecular mass of 53 kDa. The p53 protein plays a fundamental role in human cell growth and mutations in this protein are frequently associated with the formation of tumors. It is estimated that of the 6.5 million people diagnosed with one or another form of cancer each year about half have p53 mutations in their tumor cells and that the vast majority of these mutations are single point mutations. 

Defects of complex II. These have not been fully characterized in the few reported patients, and the diagnosis has often been based solely on a decrease of succinate-cytochrome c reductase activity (Fig. 42-3). However, partial complex II deficiency was documented in muscle and cultured fibroblasts from two sisters with clinical and neuroradiological evidence of Leigh s syndrome, and molecular genetic analysis showed that both patients were homozygous for a point mutation in the flavoprotein subunit of the complex [17]. This was the first documentation of a molecular defect in the nuclear genome associated with a respiratory chain disorder. 

Based on the amino acid sequence, SEs have been divided into three groups. The first group includes SEB and SEC, together with subtypes and molecular variants. The second group consists of SEA, SEE and SED. The third group comprises SEH. There are numerous point mutations within particular groups. For example, SEC isolated from humans reveals a low level of dissimilarity (>95% of similarity) if compared with bovine and ovine SEC (Mart et al., 1993). 

Yu Q, Jacquier AC, Citri Y, Hamblen M, Hall JC, Rosbash M 1987 Molecular mapping of point mutations in the period gene that stop or speed up biological clocks in Drosophila melanogaster. Proc Natl Acad Sci USA 84 784-788... 

The primary sequences of important channel peptides, such as the nicotinic acetylcholine receptors, and sodium, potassium, and calcium channels, have been determined by the innovative work of the late professor Numa and his group. " Thereafter, various structural models on the basis of empirical as well as molecular mechanics or molecular dynamics calculations were proposed " and tested by specific point mutation studies. 

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