Sequence search

What can be done by predictive methods if the sequence search fails to reveal any homology with a protein of known tertiary structure Is it possible to model a tertiary structure from the amino acid sequence alone There are no methods available today to do this and obtain a model detailed enough to be of any use, for example, in drug design and protein engineering. This is, however, a very active area of research and quite promising results are being obtained in some cases it is possible to predict correctly the type of protein, a, p, or a/p, and even to derive approximations to the correct fold. 

Translate the DNA sequence into a protein sequence, searching all six frames... 

It is worth noting that the past few years have witnessed tremendous development of web-based information resources. Notably, the PubMed search tool [4] has made the investigation of any life sciences topic much easier. It offers keyword and author (as well as structure and sequence) searches and covers a wide range of medicinal chemistry-related journals. This resource, coupled with e-journals, affords the medicinal chemist the tools to keep up with any research topics of interest. Because of the public nature of the Web, now a chemist can sometimes find critical journal articles on the Web that do not show up until much later in traditional literature sources. It is not uncommon that scientific meeting presentations can be found on the Web. Indeed, the Internet tools we have all become familiar with also have made the professional life of the medicinal chemist much easier. 

Homology screening. Using oligonucleotide probes based on known receptor sequences, search cDNA libraries for homologous sequences which may code for related receptors. The clones are then isolated and sequenced and used in expression studies to confirm the identity of the receptor. 

All samples were digested with trypsin and analyzed by cIEF in the first dimension followed by LC-MS/MS as described above. Samples were analyzed in duplicate. Sequence searching was performed using OMSSA. Analysis of the soluble fraction yielded a total of 2856 identified proteins, while the insoluble fraction yielded 3227 proteins. Combined, the fresh-frozen sample yielded 3902 protein identifications. The FFPE portion yielded 2845 protein identifications from 14,178 distinct tryptic peptide sequences, on a par with the fresh-frozen soluble fraction. Combining all identifications gave 4145 proteins. While, the soluble fraction and the FFPE extraction yielded similar numbers of protein identification, both found 25% of their respective protein set uniquely (Fig. 20.4). 

Henikoff, S. (1996). Scores for sequence searches and alignments. Curr. Opin. Struct. Biol. 6, 353-360. 

The DNA sequence of the encoding AMDase and the amino acid sequence deduced from it was compared with the data base using DNASIS (Hitachi). No significant homologies were observed with any of the sequences searched. 

The lower part shows information ofselected protein sequence. The small table shows the results of sequence search against UNIPROT(Swiss-prot/TrEMBL), nr.aa, and UniGene database see Subheading 2, items 2 and 4) using BLAST. 

There are different classes of protein sequence databases. Primary and secondary databases are used to address different aspects of sequence analysis. Composite databases amalgamate a variety of different primary sources to facilitate sequence searching efficiently. The primary structure (amino acid sequence) of a protein is stored in primary databases as linear alphabets that represent the constituent residues. The secondary structure of a protein corresponding to region of local regularity (e.g., a-helices, /1-strands, and turns), which in sequence alignments are often apparent as conserved motifs, is stored in secondary databases as patterns. The tertiary structure of a protein derived from the packing of its secondary structural elements which may form folds and domains is stored in structure databases as sets of atomic coordinates. Some of the most important protein sequence databases are PIR (Protein Information Resource), SWISS-PROT (at EBI and ExPASy), MIPS (Munich Information Center for Protein Sequences), JIPID (Japanese International Protein Sequence Database), and TrEMBL (at EBI). ... 

Most protein families are characterized by several conserved motifs. The PRINTS hngerprint database was developed to use multiple conserved motifs to build diagnostic signatures of family membership (Attwood et al., 1998). If a query sequence fails to match all the motifs in a given hngerprint, the pattern of matches formed by the remaining motifs allows the user to make a reasonable diagnosis. The PRINTS can be accessed by keyword and sequence searches at http //www.bioinf. 

For these reasons, it is important to focus on the most divergent set of superfamily members that can be identified. Although a variety of new methods have recently been developed for identification of distantly related protein sequences [see, for example, Psi-Blast (Altschul et al, 1997), methods based on Hidden Markov Models such as SAMT98 (Kar-plus et al., 1998), the Intermediate Sequence Search algorithm of Park et al., (Park et al., 1997), or the simple congruence method, Shotgun (Pegg and Babbitt, 1999)], confirmation of these relationships can be technically difficult. In some cases, three-dimensional structural information or experimental structure-function analysis will be required to pro-... 

The National Center for Biotechnology Information (NCBI). Located at the National Library of Medicine in Bethesda, MD, USA. The home of the GenBank DNA sequence database PubMed literature search engine sequence search tools (e.g., PSI-BLAST) genomic sequence navigation tools. A substantial repository of resources in all areas of bioinformatics. 

The National Institutes of Health maintains a databank called Genbank, Its address on the internet is http / /www.ncbi.njm.nih gov. Once the homepage has been displayed on the screen, one can highlight Nucleotide Sequence Search, type the name of the protein coded by the nucleotides, and access the nucleotide sequence. Alternatively, one can highlight Protein Sequence Search, type the name of the protein, and acquire the amino acid sequence. If one knows the partial DNA sequence, i e, about 50 consecutive nucleotides, one can enter the sequence and, in this way, acquire a display of any gene that contains the entered sequence. If one knows the partial amino acid sequence, i.e., about 15 consecutive amino adds, one can also enter this sequence and get a display of any polypeptide containing the entered sequence. 

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