Searching for similarity

The searching for similarity also establishes the exact location(s) of the unknown receptor sites. This may be accomplished judiciously by canying out the investigative studies imder the following two categories  

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Needleman S B and C D Wunsch 1970. A General Method Applicable to the Search for Similarities in the Amino Acid Sequences of Two Proteins. Journal of Molecular Biology 48 443-453. 

Also databases of scientific literature (such as PUBMED, MEDLINE) provide additional functionality, e.g. they can search for similar articles based on word-usage analysis. Text recognition systems are being developed that automatically extract knowledge about protein function from the abstracts of scientific articles, notably on protein-protein interactions. 

One early step in the workflow of the medicinal chemist is to computationally search for similar compounds to known actives that are either available in internal inventory or commercially available somewhere in the world, that is, to perform similarity and substructure searches on the worldwide databases of available compounds. It is in the interest of all drug discovery programs to develop a formal process to search for such compounds and place them into the bioassays for both lead generation and analog-based lead optimization. To this end, various similarity search algorithms (both 2D and 3D) should be implemented and delivered directly to the medicinal chemist. These algorithms often prove complementary to each other in terms of the chemical diversity of the resulted compounds [8]. 

In search for similar accidents with the same re-occurring deviations prior to the accident, two cases were identified here. In both cases an explosion occurred during the unloading of a tanker when a pump overheated causing a decomposition of N2O vapour, resulting in an explosion. 

Establishment of the nature of active sites for various reactions. Search for similarities and differences between the crystalline zeolites and the amorphous silica-aluminas. 

Apart from the above applications, PNA is also of interest in its own right. This quite unique DNA mimic has inspired many chemists to search for similar molecules both by making derivatives and analogues of the original PNA structure, but also by searching for novel structural motifs. 

Searches for similar protein and nucleic acid sequences Protein structures on moving 3D coordinates Sequence retrieval system for cross-referencing databases Searches for similar protein sequences Database of gene sequences... 

BLAST Chime Entrez (NCBI) FASTA GenBank (NCBI) Molecules R Us RasMol (Ras Mac) SRS (EMBL) Searches for similar protein and nucleic acid sequences Protein structures on moving 3D coordinates Sequence retrieval system for cross-referencing databases Searches for similar protein sequences Database of gene sequences Provides coordinates for protein 3D structure and manipulation Provides coordinates for protein 3D structure and manipulation Sequence retrieval system for cross referencing databases... 

The number of methods of data analysis is so large and the choices are sometimes so confusing, that a roadmap is needed for orientation (Fig. 10.5). At the top of this map are the model-based techniques that require specific and exact correlation between physical parameters and concentration, therefore calibration. At the bottom are the techniques that are model-free. They search for similarities in the response... 

However, a search for similar products in field isolates of M. tuberculosis proved fruitless. The work instead focused on a family of simple acylated trehaloses first reported by Minnikin et al.61 The structures of these acylated trehaloses were elucidated by a combination of GC-MS and H-13C-NMR spectrometry.68... 

Livingstone, D.J. and Salt, D.W., Neural networks in the search for similarity and structure-activity, in P.M. Dean (ed.) Molecular Similarity in Drug Design, Blackie Academic and Professional, Glasgow, 1995, pp. 187-214. 

The introduction of chlorpromazine transformed the way that drug treatment was regarded. Even before the disease-centred theory of its action crystallised, chlorpromazine was received with great enthusiasm. It was viewed as being superior to previous drug treatments and it inspired extensive research and publicity (Moncrieff 1999). It immediately stimulated a search for similar compounds and for possible drug treatments for depression (Lehmann Kline 1983). 

The essential aspect of computer-based analysis of concerted evolution is the search for similarity between physically separated parts of a given sequence. Two approaches can be used for such searches graphical comparison of an entire sequence with itself (or with a carefully selected test sequence) or a straightforward listing of regions of sequence similarity... 

These principles can be directly applied to chemistry. It is possible to determine similarities in amino acid sequences in myoglobin in a variety of species. The more similar the species, die closer is die relationship chemical similarity mirrors biological similarity. Sometimes die amount of information is so huge, for example in large genomic or crystallographic databases, diat cluster analysis is die only practicable way of searching for similarities. 

Needleman, S. B. Wunsch, C. D. (1970). A general method applicable to the search for similarities in the amino acid sequences of two proteins. J Mol Biol 48,443-53. 

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