Protein structure fluctuations

These methods work best at nanomolar chemical concentrations so that the focal volume contains typically 1 to 100 molecules on average. Because the method is so sensitive, it is susceptible to perturbation by background fluorescence and instrumentation fluctuations. These problems have become quite tractable during the last decade, such that FCS now supports more than 100 publications per year. A current challenging application is analysis of protein folding kinetics, protein structure fluctuations, and ultrafast chemical kinetics by new methods yet to be published. 

S. H. Northrup and J. A. McCammon, Biopolymers, 19,1001 (1980). Simulation Methods for Protein Structure Fluctuations. 

Petsko G A and Ringe D 1984 Fluctuations in protein structure from x-ray diffraction A. Rev. Biophys. Bioengng. 13 331-71... 

The influence of solvent can be incorporated in an implicit fashion to yield so-called langevin modes. Although NMA has been applied to allosteric proteins previously, the predictive power of normal mode analysis is intrinsically limited to the regime of fast structural fluctuations. Slow conformational transitions are dominantly found in the regime of anharmonic protein motion. 

Petsko, G. A., and Ringe, D., 1984. Fluctuations in protein structure from X-ray diffraction. Annual Review of Biophysics and Bioengineering 13 331 —371. 

The increased fluctuations of protein structures at elevated temperatures is reflected in the thermal expansion of proteins [433], that may contribute to the marked temperature dependence of the rate of Ca transport. 

Thus, aside from the covalently polymerized a-chain itself, the majority of protein structure is determined by weaker, noncovalent interactions that potentially can be disturbed by environmental changes. It is for this reason that protein structure can be easily disrupted or denatured by fluctuations in pH, temperature, or by substances that can alter the structure of water, such as detergents or chaotropes. 

As shown above, the intrinsic fluorescence spectra of proteins as well as coenzyme groups and probes shift within very wide ranges depending on their environment. Since the main contribution to spectral shifts is from relaxational properties of the environment, the analysis of relaxation is the necessary first step in establishing correlations of protein structure with fluorescence spectra. Furthermore, the study of relaxation dynamics is a very important approach to the analysis of the fluctuation rates of the electrostatic field in proteins, which is of importance for the understanding of biocatalytic processes and charge transport. Here we will discuss briefly the most illustrative results obtained by the methods of molecular relaxation spectroscopy. 

J. R. Lakowicz and G. Weber, Quenching of protein fluorescence by oxygen. Detection of structural fluctuations in proteins on the nanosecond time scale, Biochemistry 12, 4171-4179 (1973). 

Many lines of evidence suggest that proteins undergo structural fluctuations.(62 ) A question is how a molecule in solution can interact with a... 

In this model, whether kq is a function of the solvent viscosity depends upon the relative magnitudes of Mint) and Mext). If Mint) Mext),then kq will depend upon viscosity if Mint) > Mext), the structural fluctuations in the protein allowing penetration of the quencher determine the magnitude of M and change in bulk viscosity may not affect this rate. Simulation of protein penetration behavior suggests that the penetration rate should be extremely sensitive to the size and charge of the quencher.(65)... 

Parak, R G. 2003. Proteins in action The physics of structural fluctuations and conformational changes. Curr. Opin. Struct. Biol. 13 552-57. 

With regard to the comments just made by Professor Somorjai, it may be appropriate to note that some experimental and theoretical evidence does suggest a role for low-frequency, thermal fluctuations in protein structure in enzyme catalysis. 

Van der Waals Forces. Van der Waals interactions are of two types one attractive and one repulsive. Attractive van der Waals forces involve interactions among induced dipoles that arise from fluctuations in the electron charge densities of neighboring nonbonded atoms. Such interactions amount to 0.1-0.2 kcal/mol despite their small size, the large number of such interactions that occur when molecules come close together makes such interactions quite significant. Van der Waals forces favor close packing in folded protein structures. 

We have very briefly surveyed the types of protein motions thought to be associated with substrate recognition and catalysis. There is no a priori reason to expect that any of the structural fluctuations discussed... 

---