Primary, Secondary, and Higher-order Structures

The genetic information of living organisms is coded in DNA in the form of base pair sequences. There are four types of nucleotides, which are linked to a polynucleotide with a sugar-phosphate backbone. The arrangement of nucleotides along the one-dimensional chain is called the primary structure of DNA, which directly encodes the primary structure of proteins by means of 

Because of the rigid double helix structure (and the electrostatic repulsion between phosphate groups), the DNA chain is locally stiff, with a conformation that is almost a straight line with small thermal fluctuations. Quantitatively, this leads to a large characteristic decay length of the orientation correlation known as the persistent length lp re 50 nm in usual aqueous conditions, which is much larger than the molecular thickness of the DNA chain a = 2nm. 

1 The coupling of these two transitions on different scales is possible, which may merit future investigations. Note that helices are often adopted motifs in the secondary structure level in biopolymers, and investigating its impact on the higher-order structures is an important theme [5]. 

DNA molecules. Then, in Sect. 3.3, we demonstrate that the essential features are indeed described by a small number of material properties, such as Zp, L, and the environmental parameters. 

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Characterization of a drug substance is to include elucidation of structure. For NCEs, confirmation of structure can be provided by spectral analysis techniques and should include summary information on the potential for isomerism, the identification of stereochemistry, and/or the potential for forming polymorphs. For protein macromolecules, structural details should include information on primary, secondary, and higher-order structure, posttranslational forms, biological activity, purity, and immunochemical proper ties (when relevant). 

In particular, we can now determine the main-chain conformation of various copolypeptides (and some proteins) in the solid state from the criso and labelled natural protein can be provided. As the relation between the nitrogen shielding and the structures (primary, secondary and higher ordered structures) is clarified in the future, we will be able to get more detailed information on the structure of polypeptides and proteins in the solid state. 

This section focuses on steady and unsteady hydrodynamic modes that emerge as the rotational speed of the inner cylinder (expressed by Ta) and pressure-driven axial flow rate (scaled by Re) are varied, while the outer cylinder is kept fixed. These modes constitute primary, secondary and higher order bifurcations, which break the symmetry of the base helical Couette-Poiseuille (CP) flow and represent drastic changes in flow structure. Figure 4.4.2 presents a map of observed hydrodynamic modes in the (Ta, Re) space, and marks the domain where all of the hydrodynamic modes that interest us appear. We will return to this figure shortly. 

Structural similarities can be seen, however, when the hydropathy profiles of the tobacco and Arabidopsis ALS transit peptides are compared (not shown). This suggests that a functional transit sequence depends more on secondary or higher order structural constraints than on primary sequence information. The in vitro uptake system described above can be used to further investigate the transit peptide domain. 

The essential distinction between the approaches used to formulate and evaluate proteins, compared with conventional low molecular weight drugs, lies in the need to maintain several levels of protein structure and the unique chemical and physical properties that these higher-order structures convey. Proteins are condensation polymers of amino acids, joined by peptide bonds. The levels of protein architecture are typically described in terms of the four orders of structure [23,24] depicted in Fig. 2. The primary structure refers to the sequence of amino acids and the location of any disulfide bonds. Secondary structure is derived from the steric relations of amino acid residues that are close to one another. The alpha-helix and beta-pleated sheet are examples of periodic secondary structure. Tertiary... 

Currently, there exists an enormous and growing deficit between the number of polypeptides whose amino acid sequence has been determined and the numbers of polypeptides whose three-dimensional structure has been resolved. Given the complexities of resolving three-dimensional structure experimentally, it is not surprising that scientists are continually attempting to develop methods by which they could predict higher order structure from amino acid sequence data. Although modestly successful secondary structure predictive approaches have been developed, no method by which tertiary structure may be predicted from primary data has thus far been developed. 

Analyses of promoter sequences suggest that the basis of interaction with RNA polymerases does not reside solely in the primary structure but may also involve certain secondary and/or higher ordered structures. A number of promoters are... 

A benefit of peptide synthesis is that one can easily fine tune amino acid content (i.e. primary structure) of peptides to customize final molecular conformations, gelation times, or other molecular interactions. This allows the creation of an array of peptides with minute differences in sequences but vast differences in final properties. Characterization is important to understanding the secondary structures formed by individual peptides and, consequently, the higher order structures that are formed during gelation. To confirm and characterize second order stracture, two spectroscopic methods, circular dichroism spectroscopy (CD) and Fourier-transform infrared spectroscopy (FUR) are frequently used. Both methods examine light absorption... 

In the structures obtained from the simulations ca. 61.7 % of the carbon atoms belong to the main chain and c.a. 36.5 % to the primary branches, i.e. less than 2% appears in the branches of higher order. The lengths of the longest observed primary, secondary, tertiary branches are 28, 11, and 7, respectively. However, the average lengths of those branches are muchshorter 1.6, 2.3, and 0.3. Only one quaternary methyl branch was obtained in all the simulations. 

The primary stmcture gives rise to higher order levels of structure (secondary, tertiary, quaternary) and all enzymes have a three-dimensional folded structure of the polymer chain (or chains). This tertiary structure forms certain arrangements of amino acid groups that can behave as centers for catalytic reactions to occur (denoted as active sites). How an active site in an enzyme performs the chemical reaction is described in Vignette 4.2.1. 

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. 

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