Protein Part-4

Proteomics and Bioinformatics

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Proteomics and BioinformaticsThe total complement of proteins present at a time in a cell or cell type is known as its proteome, and the study of such large-scale data sets defines the field of proteomics, named by analogy to the related field of genomics. Key experimental techniques in proteomics include Mass Spectrometry, which allows rapid highthroughput identification of proteins and sequencing of peptides. protein microarrays, which allow the detection of the relative levels of a large number of proteins present in a cell, and two-hybrid screening, which allows the systematic exploration of protein-protein interactions. The total complement of biologically possible such interactions is known as the interactome. A systematic attempt to determine the structures of proteins representing every possible fold is known as structural genomics.The large amount of genomic and proteomic data available for a variety of organisms, including the human genome, allows researchers to efficiently identify homologous proteins in distantly related organisms by sequence alignment. Sequence profiling tools can perform more specific sequence manipulations such as restriction enzyme maps, open reading frame analyses for nucleotide sequences, and secondary structure prediction. From this data phylogenetic trees can be constructed and evolutionary hypotheses developed using special software like ClustalW regarding the ancestry of modern organisms and the genes they express. The field of bioinformatics seeks to assemble, annotate, and analyze genomic and proteomic data, applying computational techniques to biological problems such as gene finding and cladistics.

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Structure Prediction and Simulation

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Complementary to the field of structural genomics, protein structure prediction seeks to develop efficient ways to provide plausible models for proteins whose structures have not yet been determined experimentally. The most successful type of structure prediction, known as homology modeling, relies on the existence of a "template" structure with sequence similarity to the protein being modeled; structural genomics' goal is to provide sufficient representation in solved structures to model most of those that remain. Although producing accurate models remains a challenge when only distantly related template structures are available, it has been suggested that sequence alignment is the bottleneck in this process, as quite accurate models can be produced if a "perfect" sequence alignment is known. Many structure prediction methods have served to inform the emerging field of protein engineering, in which novel protein folds have already been designed. A more complex computational problem is the prediction of intermolecular interactions, such as in molecular docking and protein-protein interaction prediction.The processes of protein folding and binding can be simulated using techniques derived from molecular dynamics, which increasingly take advantage of distributed computing as in the Folding@Home project. The folding of small alpha-helical protein domains such as the villin headpiece and the HIV accessory protein have been successfully simulated in silico, and hybrid methods that combine standard molecular dynamics with quantum mechanics calculations have allowed exploration of the electronic states of rhodopsins.

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History

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Proteins were recognized as a distinct class of biological molecules in the eighteenth century by Antoine Fourcroy and others, distinguished by the molecules' ability to coagulate or flocculate under treatments with heat or acid. Noted examples at the time included albumen from egg whites, blood, serum albumin, fibrin, and wheat gluten. Dutch chemist Gerhardus Johannes Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula. The term "protein" to describe these molecules was proposed in 1838 by Mulder's associate Jons Jakob Berzelius. Mulder went on to identify the products of protein degradation such as the amino acid leucine for which he found a (nearly correct) molecular weight of 131 Da.The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study. Hence, early studies focused on proteins that could be purified in large quantities, e.g., those of blood, egg white, various toxins, and digestive/metabolic enzymes obtained from slaughterhouses. In the late 1950s, the Armour Hot Dog Co. purified 1 kg (= one million milligrams) of pure bovine pancreatic ribonuclease A and made it freely available to scientists around the world.
Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding, an idea first put forth by William Astbury in 1933. Later work by Walter Kauzmann on denaturation, based partly on previous studies by Kaj Linderstorm-Lang, contributed an understanding of protein folding and structure mediated by hydrophobic interactions. In 1949 Fred Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, colloids, or cyclos. The first atomic-resolution structures of proteins were solved by X-ray crystallography in the 1960s and by NMR in the 1980s. As of 2006, the Protein Data Bank has nearly 40,000 atomic-resolution structures of proteins. In more recent times, cryo-electron microscopy of large macromolecular assemblies and computational protein structure prediction of small protein domains are two methods approaching atomic resolution.

Text Source: Wikipedia Liscence NGU