Motion in proteins

Hayward, S., Kitao, A., Berendsen, H.J.C. Model-free methods to analyze domain motions in proteins from simulation A comparison of normal mode analysis and molecular dynamics simulation of lysozyme. Proteins 27 (1997) 425-437. 

Elamrani et al. 1996] Elamrani, S., Berry, M.B., Phillips Jr., G.N., McCammon, J.A. Study of Global Motions in Proteins by Weighted Masses Molecular Dynamics Adenylate Kinase as a Test Case. Proteins 25 (1996) 79-88 [Elcock et al. 1997] Elcock, A.H., Potter, M.J., McCammon, J.A. Application of Poisson-Boltzmann Solvation Forces to Macromolecular Simulations. In Computer Simulation of Biomoleeular Systems, Vol. 3, A.J. Wilkinson et al. eds., ESCOM Science Publishers B.V., Leiden... 

Normal mode analysis exists as one of the two main simulation techniques used to probe the large-scale internal dynamics of biological molecules. It has a direct connection to the experimental techniques of infrared and Raman spectroscopy, and the process of comparing these experimental results with the results of normal mode analysis continues. However, these experimental techniques are not yet able to access directly the lowest frequency modes of motion that are thought to relate to the functional motions in proteins or other large biological molecules. It is these modes, with frequencies of the order of 1 cm , that mainly concern this chapter. 

Experimental approaches to direct characterization of the conformational exchange motions in proteins have been suggested earlier [67-69]. The most recent methods [66, 70-73] are based on a relaxation-compensated version of CPMG that alleviates the previous restriction on the duration of the refocusing delay due to evolution of magnetization from scalar couplings and dipole-dipole cross-correlations. 

R. M. Levy and R. P. Sheridan, Combined effect of restricted rotational diffusion plus jumps on nuclear magnetic resonance and fluorescence probes of aromatic ring motions in proteins, Biophys. J. 41, 217-221 (1983). 

Table 2.1. Intramolecular Motions in Proteins and the Values of the Parameters that Characterize Them Mass of Structural Element (m), Amplitude (A), Characteristic Time (r), Activation Energy ( ,), and Cross-Correlation (< X1-ZX2 ...

None of the methods currently used to study molecular dynamics can span the whole time range of motions of interest, from picoseconds to seconds and minutes. However, the structural resolution of a method is of equal importance. A method has to not only provide information about the existence of motions with definite velocities but also to identify what structural element is moving and what is the mechanism of motion. Computer simulation of molecular dynamics has proved to be a very important tool for the development of theories concerning times and mechanisms of motions in proteins. In this approach, the initial coordinates and forces on each atom are input into the calculations, and classical equations of motions are solved by numerical means. The lengthy duration of the calculation procedure, even with powerful modem computers, does not permit the time interval investigated to be extended beyond hundreds of picoseconds. In addition, there are strong... 

The results obtained show that the dipole-relaxational motions in protein molecules are really very retarded as compared to such motions in the environment of aromatic molecules dissolved in liquid solvents (where they occur on a time scale of tens of picoseconds).(82) Dipole-relaxational motions on the nanosecond time scale have been observed for a variety of proteins. For example, such motions were recorded for apohemoglobin and bovine serum albumin0 04 105) labeled with the fluorescent probe 2,6-TNS. 

C. K. Woodward and B. D. Hilton, Hydrogen exchange kinetics and internal motions in proteins, Annu. Rev. Biophys. Bioeng. 8, 99-128 (1979). 

Motions in Proteins Frank R. N. Gurd and T. Michael Rothgeb... 

Tirion, M. (1996) Large Amplitude Elastic Motions in Proteins from a Single-Parameter, Atomic Analysis. Phys. Rev. Lett. 77,1905-1908. 

Garcia, A.E. Large-amplitude nonlinear motions in proteins. Phys. Rev. Lett. 1992, 68, 2696-9. 

Fig. 5. Types of motion in proteins detected by nmr. Rotation about methyl groups is easily detected from threefold symmetry and is rapid. Rotation or flipping about the C(J—Cy bonds of tyrosine or phenylalanine has been observed readily (see text) because of the twofold symmetry of the aromatic ring. Rotation of more complex side chains is more difficult to define because of the lack of symmetry.

Motion, in proteins 81 Mouse, genome 12 mRNA 5,230,257,536 splicing of 11 Mucins 181,182... 

Conformational motions in proteins span at least 14 orders of magnitude in terms of time scales, from picoseconds to minutes/hours (Scheme 1). 

Some internal motions of proteins can be described quite simply. These include the localized vibrations within covalently bonded groups and also the elastic vibrations that involve coherent small-amplitude displacements of larger portions of the molecule. But generally, motions in proteins are more complex,... 

Motions in proteins correspond to excursions on this energy landscape, and may be correspondingly complex. Even the simple motions mentioned at the outset of this section will be perturbed by transitions over barriers in the protein s energy landscape e.g., the localized vibrations of a covalently bonded group will differ to some extent, depending on which energy well in the landscape the biopolymer resides in. 

Interesting applications of anisotropy decays for proteins often develop not from tumbling of the protein as a whole, but from other reorientational degrees of freedom. These motions may include protein domain motions or segmental motions in proteins and peptides. The anisotropy decay in this case is non-single-exponential (see Fig. 4c) and takes the form ... 

Most of the information on interdomain motions come from high-resolution crystal structures several reviews are available (Janin and Wodak 1983 Bennett andHuber 1984 Gerstein et al. 1994). Calculations ofhinge bending modes and domain motions in proteins other than lysozyme have been made. They include antibody molecules where the interdomain motions occur on a nanosecond time scale (McCammon and Karplus 1977 Oi et al. 1984), 1-arabinose-binding protein (Mao et al. 1982), liver alcohol dehydrogenase (Colona-Cesari et al. 1986) and the mouse... 

Bennett, W. S. and Huber, R. (1984) Structural and Functional Aspects of Domain Motions in Proteins, Crit. Rev. Biochem. 15, 291-384. 

P. Dauber-Osguthorpe, D. J. Osguthorpe, P. S. Stem and J. Moult, Low frequency motion in proteins comparison of normal mode and molecular dynamics of streptomyces griseus protease A, J. Comput. Phys., 151(1), 169-189 (1999). 

RllO R. Sharp, L. Lohr and J. Miller, Paramagnetic NMR Relaxation Enhancement. Recent Advances in Theory , p. 115 Rill V. A. Mandelshtam, FDM. The Filter Diagonalization Method for Data Processing in NMR Experiments , p. 159 R112 D. M. Korzhnev, M. Billeter, A. S. Arseniev and V. Y. Orekhov, NMR Studies of Brownian Tumbling and Internal Motions in Proteins , p. 197 R113 M. Pons and O. Millet, Dynamic NMR Studies of Supramolecular Complexes , p. 267... 

There is no straightforward and completely rigorous procedure for determining the relative combinations of the various relaxation mechanisms, except where one mechanism clearly dominates (e.g., if the maximum possible nuclear Overhauser effect (NOE) for a resonance is obtained, dipolar relaxation must dominate its relaxation or an increase in relaxation rate in proportion to the square of the applied field must be due to chemical shift anisotropy). Hence, the study of molecular motion in proteins from relaxation data is performed most readily on nuclei directly bonded to H, and so principally relaxed via dipole-dipole interactions (see Section 4(e)(iii)). 

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