Proteins, backbones, secondary structures

The polypeptide chains of proteins do not remain in a flat plane. Instead, as a protein is formed, the polypeptide chain starts to twist and curl up. It folds and coils like a rope that can be bundled in many different shapes. This coiling and folding determines the protein s secondary structure. The secondary structure is maintained by chemical bonds between the carboxyl groups and the amino groups in the polypeptide backbone. There are many secondary structure patterns, but the two most common are the a-helix, and the p-sheet. 

Combined SAXS/Circular dichroism beamline. Biological macromolecules, such as proteins, carbohydrates and nucleic acids, are composed of many optically active or chiral units that exhibit large Circular Dichroism (CD) signals. CD spectroscopy has therefore been used extensively in the study of proteins, where asymmetric carbon atoms in their amino acid backbone give rise to a CD spectrum. The shape of the spectrum depends on the protein s secondary structure content and allows the proportions of helix, beta structure, turns and random to be determined. 

The primary structure of a protein is the sequence of the amino acid units in the protein. The secondary structure is the shape that the backbone of the molecule (the chain containing peptide bonds) assumes. The two most common secondary structures are the a-helix and the /3-pleated sheet. An a-helix is held together by the intramolecular hydrogen bonds that form between the N-H group of one amino acid and the oxygen atom in the third amino acid down the chain from it. 

Many types of forces and interactions play a role in holding a protein together in its correct, native conformation. Some of these forces are covalent, but many are not. The primary structure of a protein—the order of amino acids in the polypeptide chain—depends on the formation of peptide bonds, which are covalent. Higher-order levels of structure, such as the conformation of the backbone (secondary structure) and the positions of all the atoms in the protein (tertiary structure), depend on noncovalent interactions. If the protein consists of several subunits, the interaction of the subunits (quaternary structure. Section 4.5) also depends on noncovalent interactions. Noncovalent stabilizing forces contribute to the most stable structure for a given protein, the one with the lowest energy. 

The original Karplus equation has been subjected to continuous modifications and reparameterizations in order to embrace a vast number of different nuclear pairs on diflerent molecular environments [6—23]. The scope of this chapter is to discuss the use of Karplus-type equations for the description of the dihedral dependence of /-couplings and to gather the most relevant data available to date, specifically devoted to the characterization of backbone (secondary structure) and side-chain conformations of proteins, /-couplings over one ( J) and two (/) bond ones are not as highly used as the -couplings for structural determination, but notable exceptions will also be covered. 

The visuahzation of hundreds or thousands of connected atoms, which are found in biological macromolecules, is no longer reasonable with the molecular models described above because too much detail would be shown. First of aU the models become vague if there are more than a few himdied atoms. This problem can be solved with some simplified models, which serve primarily to represent the secondary structure of the protein or nucleic acid backbone [201]. (Compare the balls and sticks model (Figure 2-124a) and the backbone representation (Figure 2-124b) of lysozyme.)... 

Figure 7-16. Superimpasition of the X-ray structure of the tetracycline repressor class D dimer (dark, protein database entry 2TRT) with the calculated geometrical average of a 3 ns MD simulation (light trace). Only the protein backbone C trace Is shown, The secondary structure elements and the tertiary structure are almost perfectly reproduced and maintained throughout the whole production phase of the calculation,...

The comparison of both data sources qualitatively shows a similar picture. Regions of high mobflity are located especially between the secondary structure elements, which are marked on the abscissa of the plot in Figure 7-17. Please remember that the fluctuations plotted in this example also include the amino acid side chains, not only the protein backbone. This is the reason why the side chains of large and flexible amino acids like lysine or arginine can increase the fluctuations dramatically, although the corresponding backbone remains almost immobile. In these cases, it is useful to analyze the fluctuations of the protein backbone and side chains individually. 

Analysis and prediction of side-chain conformation have long been predicated on statistical analysis of data from protein structures. Early rotamer libraries [91-93] ignored backbone conformation and instead gave the proportions of side-chain rotamers for each of the 18 amino acids with side-chain dihedral degrees of freedom. In recent years, it has become possible to take account of the effect of the backbone conformation on the distribution of side-chain rotamers [28,94-96]. McGregor et al. [94] and Schrauber et al. [97] produced rotamer libraries based on secondary structure. Dunbrack and Karplus [95] instead examined the variation in rotamer distributions as a function of the backbone dihedrals ( ) and V /, later providing conformational analysis to justify this choice [96]. Dunbrack and Cohen [28] extended the analysis of protein side-chain conformation by using Bayesian statistics to derive the full backbone-dependent rotamer libraries at all... 

FIGURE 5.8 Two structural motifs that arrange the primary structure of proteins into a higher level of organization predominate in proteins the a-helix and the /3-pleated strand. Atomic representations of these secondary structures are shown here, along with the symbols used by structural chemists to represent them the flat, helical ribbon for the a-helix and the flat, wide arrow for /3-structures. Both of these structures owe their stability to the formation of hydrogen bonds between N—H and 0=C functions along the polypeptide backbone (see Chapter 6). 

Whereas the primary structure of a protein is determined by the covalently linked amino acid residues in the polypeptide backbone, secondary and higher... 

R I he secondary structure of a protein describes how segments of the peptide backbone orient into a regular pattern. 

The secondary structure of a protein is determined by hydrogen bonding between CDO and N—H groups of the peptide linkages that make up the backbone of the protein. Hydrogen bonds can exist within the same protein... 

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