Fluctuating secondary structure

The native conformation is assumed to be the result of a structural self-organization process which starts in various regions of the chain independently and simultaneously. The idea behind this mechanism is the initiation of protein folding by developing local, fluctuating secondary structures as a consequence of short-range interactions... 

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. 

Many experiments have been carried out by using this setup the stretching of single DNA molecules, the unfolding of RNA molecules or proteins, and the translocation of molecular motors (Fig. 2). Here we focus our attention on force experiments where mechanical work can be exerted on the molecule and nonequilibrium fluctuations are measured. The most successful studies along this line of research are the stretching of small domain molecules such as RNA [83] or protein motifs [84]. Small RNA domains consist of a few tens of nucleotides folded into a secondary structure that is further stabilized by tertiary interactions. Because an RNA molecule is too small to be manipulated with micron-sized beads, it has to be inserted between molecular handles. These act as polymer spacers that avoid nonspecific interactions between the bead and the molecule as well as the contact between the two beads. 

A large amount of secondary structure, but any tertiary structure appears to be fluctuating and many residues are in contact with water ... 

In any case, the Ca RMS deviations for the high pH simulation do indeed remain relatively low, particularly for the core of the molecule (i.e., disregarding the N-terminus), whereas the structure deviates more dramatically at low pH (Fig. 8A). The heightened mobility of the N-terminal region is evident in the Ca RMS fluctuations about tbe MD mean structure over tbe last 2.5 ns of each simulation (Fig. 8B). At high pH, the fluctuations about the secondary structure are low, and the only high values correspond to the N-terminus and the loop between HB and HC. Various snapshots from the two simulations are overlaid in Fig. 9 to illustrate the nature and extent of the motion. The low, and quite normal, mobility of the structured part of the molecule is in agreement... 

In a related work, NMR spectra of [3- C]Ala- and [l- C]Val-labelled bacteriorhodopsin and a variety of its mutants have also been reported. These studies were undertaken in order to clarify contributions of the extracellular Glu residues to the conformation and dynamics of bacteriorhodopsin. Significant dynamic changes were induced for the triple or quadruple mutants, as shown by broadened NMR peaks of [l- C]Val-labelled proteins. These changes were due to acquired global fluctuation motions of the order of 10 -10" s as a result of disorganised trimeric form. It was concluded that the Glu residues at the extracellular surface play an important role in maintaining the native secondary structure of bacteriorhodopsin in the purple membrane. 

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