Local flexibility

Balazs, A. 1991. Notes on the Local Flexibility of the Polypeptide Backbone Part I. Mean amplitudes of thermal motions in the dipeptide model. J. Mol. Struct. 245, 111-117. 

The major structural factors that influence the reactivity of aspartic acid residues are i) conformational aspects of the peptide, particularly the local flexibility of the peptide chain as dictated by primary, secondary, and tertiary structure, and ii) the amino acid sequence (i.e., the nature of the adjacent residues). Most of the available evidence concerns the influence of adjacent residues, as discussed in this section. 

The facilitating effect of glycine is ascribed to the local flexibility induced by the absence of a side chain. This implies that the cleavage of... 

The influence of secondary structure on reactions of deamidation has been confirmed in a number of studies. Thus, deamidation was inversely proportional to the extent of a-helicity in model peptides [120], Similarly, a-hel-ices and /3-turns were found to stabilize asparagine residues against deamidation, whereas the effect of /3-sheets was unclear [114], The tertiary structure of proteins is also a major determinant of chemical stability, in particular against deamidation [121], on the basis of several factors such as the stabilization of elements of secondary structure and restrictions to local flexibility, as also discussed for the reactivity of aspartic acid residues (Sect. 6.3.3). Furthermore, deamidation is markedly decreased in regions of low polarity in the interior of proteins because the formation of cyclic imides (Fig. 6.29, Pathway e) is favored by deprotonation of the nucleophilic backbone N-atom, which is markedly reduced in solvents of low polarity [100][112],... 

Macromolecules display continuous motions. These motions can be of two main types the molecule can rotate on itself, following the precise axis of rotation, and it can have a local flexibility. Local flexibility, also called internal motions, allows different small molecules, such as solvent molecules, to diffuse along the macromolecule. This diffusion is generally dependent on the importance of the local internal dynamics. Also, the fact that solvent molecules can reach the interior hydrophobic core of macromolecules such as proteins clearly means that the term hydrophobicity should be considered as relative and not as absolute. Internal dynamics of proteins allow and facilitate a permanent contact between protein core and the solvent. Also, this internal motion permits small molecules such as oxygen to diffuse within the protein core. Since oxygen is a collisional quencher, analyzing the fluorescence data in the presence of different oxygen concentrations yields information on the internal dynamics of macromolecules. 

In the work of Zachmann et al. new approaches to the quantification of surface flexibility have been suggested. The basis data for these approaches are supplied by molecular dynamics (MD) simulations. The methods have been applied to two proteins (PTI and ubiquitin). The calculation and visualization of the local flexibility of molecular surfaces is based on the notion of the solvent accessible surface (SAS), which was introduced by Connolly. For every point on this surface a probability distribution p(r) is calculated in the direction of the surface normal, i.e., the rigid surface is replaced by a soft surface. These probability distributions are well suited for the interactive treatment of molecular entities because the former can be visualized as color coded on the molecular surface although they cannot be directly used for quantitative shape comparisons. In Section IV we show that the p values can form the basis for a fuzzy definition of vaguely defined surfaces and their quantitative comparison. 

Localizing Flexibility within the Target Site of DNA-bending Proteins... 

The properties of the surplus segment probability p and the effective constraint coordination number z are less well established. It seems possible that p will dep d on polymer species to some extent, since loop projection may be easier for a more locally flexible chain. Weak dependences on concentration and temf rature are likely for the same reason. On the other hand, z characterizes the topology on a fairly large scale and therefore may be virtually a universal constant. Diese however are only some speculations. Values of p and z can be established by various experiments, p from the elastic properties of networks and also from the relaxation of star polymers, z from relative relaxation rates of linear and star molecules in liquids and networks and also from measurements of diffusion rates of stars in linear chain liquids. The adequacy of the... 

Besides being enormously expanded and spheroidal, the mucins also appear very flexible evidence for this derives from the ease with which these molecules are deformed with shear, as shown in streaming-birefringence experiments, from the concentration dependence of viscosity, and the temperature-dependence of sedimentation coeflScients. Mikkelsen and co-workers confirmed these observations by using the dependence on field strength of electric birefringence relaxation-phenomena. Evidence for local flexibility in the carbohydrate side-chains has come from, for example, n.m.r.-spectral studies. ... 

The essential role of protein structure dynamics as a mechanistic consideration in proton transport has focused attention on amino acids such as proline (3, 9), which can confer localized flexibility within and between helical segments. Except for the unique case of bacteriorhodopsin, which is amenable to spectroscopic examination (10), little is known about the nature of molecular dynamics in transport enzymes. 

Since calcofluor binds to the pocket of a i-acid glycoprotein, the observed thermal quenching could also be the result of a local flexibility that originates from both the carbohydrate residues surrounding the fluorophore and the amino acids of the glycosylation site within the pocket. In fact, flexibility and local motions were observed for Trp residues in both sialylated and asialylated a i-acid glycoprotein. 

Dynamic information in addition to the static structure, local flexibilities can be measured for the complex and the free components to yield a more accurate picture of the intermolecular interactions. 

Gorovits, B. M., aod Horowitz, P. M., 1995, The molecular chaperonin q 60 displays local flexibility that is lednoed after Unding with an unfolded protein, / BioL C TML 276t 13057-13061... 

Majumdar, R., Manikwar, P., Hickey, J.M., et al. (2013) Effects of srdts from the Hofmeister series on the conformational stabihty, aggregation propensity, and local flexibility of an IgGl monoclonal antibody. Biochemistry, 52 (19), 3376-3389. 

---