Protein folding threading

Ithough knowledge-based potentials are most popular, it is also possible to use other types potential function. Some of these are more firmly rooted in the fundamental physics of iteratomic interactions whereas others do not necessarily have any physical interpretation all but are able to discriminate the correct fold from decoy structures. These decoy ructures are generated so as to satisfy the basic principles of protein structure such as a ose-packed, hydrophobic core [Park and Levitt 1996]. The fold library is also clearly nportant in threading. For practical purposes the library should obviously not be too irge, but it should be as representative of the different protein folds as possible. To erive a fold database one would typically first use a relatively fast sequence comparison lethod in conjunction with cluster analysis to identify families of homologues, which are ssumed to have the same fold. A sequence identity threshold of about 30% is commonly... 

B Rost, R Schneider, C Sander. Protein fold recognition by prediction-based threading. J Mol Biol 270 471-480, 1997. 

The first requirement for threading is to have a database of all the known different protein folds. Eisenberg has used his own library of about 800 folds, which represents a minimally redundant set of the more than 6000 structures deposited at the Protein Data Bank. Other groups use databases available on the World Wide Web, where the folds are hierarchically ordered according to structural and functional similarities, such as SCOP, designed by Alexey Murzin and Cyrus Chothia in Cambridge, UK. 

Vendruscolo M, Najmanovich R, Domany E. Can a pairwise contact potential stabilize native protein folds against decoys obtained by threading Proteins 2000 38 134-48. 

Another approach is to map the arrangement of secondary structural elements onto the known tertiary structures of other proteins. Currently, approximately one hundred unique protein folds have been identified. There is some question as to if this is an upper limit. If this is indeed the case, then the protein of unknown structure must adopt a known topological fold. The secondary structural elements are mapped onto the template of the different known protein structures. The best fits, as judged by the environmental factors (solvent accessibility) of the individual amino acids, are then further analyzed as probable folds. This procedure is referred to as threading the secondary elements into three-dimensional structures [28],... 

D. T. Jones, R. T. Miller, J. M. Thornton. Successful protein fold recognition by optimal sequence threading validated by rigorous blind testing. Proteins. 1995, 23, 387-397. 

Firth, J. Li, C. W. Murray. Protein fold recognition by threading comparison of algorithms and analysis of results. Prot. Eng. 1995, 8, 1197-1204. 

Jones, D. T., et al., Successful recognition of protein folds using threading methods biased by sequence similarity and predicted secondary structure. Proteins, 1999. 37(S3) p. 104-111. 

Several methods have been developed for this purpose. These include (a) comparative or homology modeling, (b) threading method or fold recognition, (c) ab initio method, and (d) visualization of protein folding by computer simulation. 

Threading If the sequence of a protein is completely dissimilar from the proteins of which the structure is known, structure prediction is often still possible by threading the sequence through a library of protein folds. All amino acids are evaluated and scored at all positions of this fold library and a best fold is chosen. It is estimated that 35% of all protein folds are currently known, but this percentage should rapidly increase because of structural genomics efforts. 

THREADER 3 User Guide Protein Fold Recognition by Threading, Version 3 Manual, David... 

Another of the successful methods that is based on a reverse approach relies on protein fold recognition by threading (31). This method takes advantage of the fact that the number of folds is limited. Instead of tr5nng to predict the fold of the protein on the basis of the amount of free energy, the method determines whether a given sequence can be fitted to a known fold. As the number of folds (Fig. 3) appears to be finite, it provides a way to look for the structure of new proteins using known folds. Another method for the prediction of three-dimensional structures of proteins is based on the in silico assembly of protein structure from shorter structural elements with more defined structures (32). 

FIG. 2.2 The three threads of information and structure in life DNA, RNA, and protein. Proteins fold into three-dimensional structures that can carry out chemistry inside, outside, and on the surface of cells. 

These threaded CDs are supposed to play a supplementary role to control the structure of poly(8-VL) during polymerization. The CDs threaded by the poly(8-VL) prevented the polymer chain from entangling with itself or with another polymer chain so as to maintain the propagating state of the polyester. These processes are similar to those of chaperone proteins in biological systems that aid protein folding and allow the formation of functional proteins. CDs showed the activation and transformation of monomers analogous to enzymes and also protein-like refolding activity as artificial chaperones. ... 

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