Macromolecules retrieval

In general, the mechanism of heat and alkaline solution for DNA extraction may be based upon a hypothesis, previously proposed for the AR technique.32 Strong alkaline solution may denature and hydrolyze proteins, resulting in breaking cell and nuclear membranes as well as disrupting cross-linkages due to formalin fixation. It is no surprise to observe the similarity between retrieval of nucleic acid and retrieval of protein (antigen) based on a similar chemical reaction of formaldehyde with these two kinds of macromolecules (Fig. 3.1).15"19... 

The Protein Data Bank (PDB http //www.pdb.org) is the worldwide repository of three-dimensional structural data of biological macromolecules, such as proteins and nucleic acids (Berman et al. 2003). The Protein Data Bank uses several text file-based formats for data deposition, processing, and archiving. The oldest of these is the Protein Data Bank format (Bernstein 1977), which is used both for deposition and for retrieval of results. It is a plain-text format whose main part, a so-called primary structure section, contains the atomic coordinates within the sequence of residues (e.g., nucleotides or amino acids) in each chain of the macromolecule. Embedded in these records are chain identifiers and sequence numbers that allow other records to reference parts of the sequence. Apart from structural data, the PDB format also allows for storing of various metadata such as bibliographic data, experimental conditions, additional stereochemistry information, and so on. However, the amount of metadata types available is rather limited owing to the age of the PDB format and to its relatively strict syntax rules. 

The PDB [7] covers biological macromolecules (proteins and nucleic acids) for which crystallographic results have been directly deposited with the compilers. The database currently contains 655 entries. Applications software is not distributed with the PDB. However, the data bank has been recast in a variety of forms for search and retrieval purposes [8,9]. Many molecular modelling systems (both commercial and academic in origin) can also read the PDB format. The database is compiled at the Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973, USA. 

For macromolecules such as proteins, the numbers of atoms that compose molecules are huge, therefore the crystal cells contain large numbers of atoms. It is not possible to apply the methods for small molecules, such as the direct method or Patterson map searching, in the structure determinations of proteins. The methods for retrieving the phases of protein crystal diffractions are molecular replacement, isomorphous replacement and anomalous scattering. In recent years, the direct method, which has been widely and successfully used in the determination of small-molecule structures, has also been applied in protein crystallography. 

D similarity searching is analogous to 2D similarity searching, and involves the retrieval of all 3D models in a CIR system that are similar to the 3D shape and atomic character of the query model. Although more recently developed, 3D similarity search has already spawned two major research threads - one for small organic molecules, and one for macromolecules. In either case, the query is exactly comprised of an entire 3D model. The definition similar in the context of 3D similarity is even more fraught with diversity than is 2D similarity, and this continues as a topic of research. 

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