Secondary protein structure loop conformation

RNA structures, compared to the helical motifs that dominate DNA, are quite diverse, assuming various loop conformations in addition to helical structures. This diversity allows RNA molecules to assume a wide variety of tertiary structures with many biological functions beyond the storage and propagation of the genetic code. Examples include transfer RNA, which is involved in the translation of mRNA into proteins, the RNA components of ribosomes, the translation machinery, and catalytic RNA molecules. In addition, it is now known that secondary and tertiary elements of mRNA can act to regulate the translation of its own primary sequence. Such diversity makes RNA a prime area for the study of structure-function relationships to which computational approaches can make a significant contribution. 

The first step, as alluded to above, is the development of possible loop conformations which connect the regions of secondary structure The loops which do not fit into the well-defined category of a-helices or (1-sheets have been fairly well characterized using the data base of proteins for which the three-dimensional structure is known [15,16], The identification of specific loop conformations provides insight into the possible orientations, or at least provides limitations on the possible orientations, of the various secondary structural elements. The second step is then analysis of the array of amino acids within the secondary structural elements with attention to the environment in which the amino acids would be found. It is clear that a cluster of hydrophobic amino acids would not likely be projecting into the aqueous solution, and more likely projecting into the core of the protein. This analysis provides additional restrictions to the number of possible arrangements in which the secondary structural elements may be found. 

Aromatic Amino Acids (Histidine, Tryptophan and Tyrosine). Histidine residues are highly susceptible to oxidation, as shown for human growth hormone [65] and relaxin [66]. The resulting degradation products are aspartic acid, asparagines, and 2-oxo-histidine [65, 67]. Metal catalyzed oxidation of histidine may alter the secondary/tertiary structures of proteins. As has been demonstrated, oxidation of the human relaxin histidine which exists in an extended loop that joins two a-helices, alters the protein conformation, resulting in pH-dependent protein aggregation and precipitation [66, 68]. 

GA s have received much attention in recent years. In chemistry, they can be used for a search in conformational space which very often involves combinations of many parameters. In particular, there were several attempts to use them for protein structure prediction (reviewed in 48). Recently, GA s were suggested to use in three rather different aspects of RNA structurerconformational search for stem-loop structures 49), prediction of optimal and suboptimal secondary structures 50) and simulation of RNA folding pathways 44,45). In the case of RNA folding simulation, a GA is also very attractive because it allows to simulate the process, in addition to obtaining a final solution. 

Generally, less than half of the protein s backbone is arranged in a defined secondary structure—an a-helix or a j8-pleated sheet (Figure 22.10). Most of the rest of the protein, though highly ordered, is nonrepetitive and therefore difficult to describe. Many of these ordered polypeptide fragments are said to be in coil or loop conformations. 

Homologous proteins have similar three-dimensional structures. They contain a core region, a scaffold of secondary structure elements, where the folds of the polypeptide chains are very similar. Loop regions that connect the building blocks of the scaffolds can vary considerably both in length and in structure. From a database of known immunoglobulin structures it has, nevertheless, been possible to predict successfully the conformation of hyper-variable loop regions of antibodies of known amino acid sequence. 

Approximately one half of an average globular protein is organized into repetitive structures, such as the a-helix and/or 3-sheet. The remainder of the polypeptide chain is described as having a loop or coil conformation. These nonrepetitive secondary structures are not... 

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