Helix formers

Different side chains have been found to have weak but definite preferences either for or against being in a helices. Thus Ala (A), Glu (E), Leu (L), and Met (M) are good a-helix formers, while Pro (P), Gly (G), Tyr (Y), and Ser (S) are very poor. Such preferences were central to all early attempts to predict secondary structure from amino acid sequence, but they are not strong enough to give accurate predictions. 

It is well known that native collagen containes tripeptide sequences, which alone are not capable of building up a triple helix (e.g. Gly-Pro-Leu, Gly-Pro-Ser) when they exist as homopolypeptides. The synthesis of threefold covalently bridged peptide chains opens up the possibility of investigating the folding properties of such weak helix formers, because the bridging reduces the entropy loss during triple-helix formation and thereby increases the thermodynamic stability of the tertiary structure. Therefore, we have... 

Aim to characterize amino acids and templates as Helix Former <== Helix Compatible ==> Helix Breaker... 

The most frequently used predictive method for secondary structures was developed by Chou and Fasman. They proposed that an a helix is present where four of six adjacent amino acids are a helix formers and if their average Pa > 1.0 and their P < 1. The a helix continues until a Pro residue is reached or the average P of four consecutive residues is less than 1. A pleated sheet is preferred when three of five consecutive residues are pleated sheet formers, where their average Pp> 1.04 and their Pa < 1. Again, this conformation is continued until the average P of four adjacent residues is less than one. A turn is encountered where four adjacent amino adds are turn formers. The Chou-Fasman method, as well as others, are not perfect, but they do provide a starting point from which... 

In the case of proline, the amide group is part of a five-membered ring and rotation about the C-N bond is not possible. Therefore, proline is considered a helix breaker and is rarely found in helices. If proline is found in an a helix, a bend or kink in the helix is usually observed at that point. Alanine, glutamic acid, leucine, and methionine are good helix formers, while proline, glycine, tyrosine, and serine are not. 

Can one predict the secondary structure of proteins by using this knowledge of the conformational preferences of amino acid residues Predictions of secondary structure adopted by a stretch of six or fewer residues have proved to be from about 60% to 70% accurate. What stands in the way of more accurate prediction Note that the conformational preferences of amino acid residues are not tipped all the way to one structure (see Table 2.3). For example, glutamate, one of the strongest helix formers, prefers a helix to p strand by only a factor of two. The preference ratios of most other residues are smaller. 

Different amino acids favor the formation of alpha helices, beta pleated sheets, or loops. The primary sequences and secondary structures are known for over 1,000 different proteins. Correlation of these sequences and structures revealed that some amino acids are found more often in alpha helices, beta sheets, or neither. Helix formers include alanine, cysteine, leucine, methionine, glutamic acid, glutamine, histidine, and lysine. Beta formers include valine, isoleucine, phenylalanine, tyrosine, tryptophan, and threonine. Serine, glycine, aspartic acid, asparagine, and proline are found most often in turns. 

On the other hand, the equilibrium constant K indicates the tendency to form helical or nonhelical states. K values in excess of unity denote helix formers K values much less than unity, conversely, indicate coil-forming sequences. With proteins, proline, serine, glycine, and aspartine, for example, are typical helix breakers. Lysine, thyrosine, aspartic acid, threonine, arginine, cysteine, and phenyl alanine act as neither helical breakers or formers, whereas all other a-amino acids are typical helix formers. 

The information measure was estimated from statistical analysis of known structures. Robson and Suzuki (1976) considered 25 proteins (i.e., about 4500 residues). Directional information was represented graphically for the different residues. In Fig. 4.7 examples are given for four amino adds taken in the classification of Lewis and co-workers (1971) (i.e., Gly and Pro as helix breakers, Glu as helix former, and Arg as helix indifferent). In Fig, 4.7, the residue considered is taken as zero. Information at —4 is the information which the named residue transmits to any residue, 4 residues away along the sequence in the N-terminal direction independently of the nature of this residue. The information for an a helix, extended structure, and turn was evaluated. 

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