Nucleic acid-protein systems, relaxation

The use of computer simulations to study internal motions and thermodynamic properties is receiving increased attention. One important use of the method is to provide a more fundamental understanding of the molecular information contained in various kinds of experiments on these complex systems. In the first part of this paper we review recent work in our laboratory concerned with the use of computer simulations for the interpretation of experimental probes of molecular structure and dynamics of proteins and nucleic acids. The interplay between computer simulations and three experimental techniques is emphasized (1) nuclear magnetic resonance relaxation spectroscopy, (2) refinement of macro-molecular x-ray structures, and (3) vibrational spectroscopy. The treatment of solvent effects in biopolymer simulations is a difficult problem. It is not possible to study systematically the effect of solvent conditions, e.g. added salt concentration, on biopolymer properties by means of simulations alone. In the last part of the paper we review a more analytical approach we have developed to study polyelectrolyte properties of solvated biopolymers. The results are compared with computer simulations. 

In liquid-state NMR, spin relaxation due to cross-correlation of two anisotropic spin interactions can provide useful information about molecular structure and dynamics. These effects are manifest as differential line widths or line intensities in the NMR spectra. Recently, new experiments were developed for the accurate measurement of numerous cross-correlated relaxation rates in scalar coupled multi-spin systems. The recently introduced concept of transverse relaxation optimized spectroscopy (TROSY) is also based on cross-correlated relaxation. Brutscher outlined the basic concepts and experimental techniques necessary for understanding and exploiting cross-correlated relaxation effects in macromolecules. In addition, he presented some examples showing the potential of cross-correlated relaxation for high-resolution NMR studies of proteins and nucleic acids. 

Transverse Relaxation Optimized Spectroscopy (TROSY). - TROSY and CRINEPT are new techniques for solution NMR studies of molecular and supramolecular structures. They allow the collection of high-resolution spectra of structures with molecular weights >100 kDa, significantly extending the range of macromolecular systems that can be studied by NMR in solution. TROSY has already been used to map protein-protein interfaces, to conduct structural studies on membrane proteins and to study nucleic acid conformations in multimolecular assemblies. A number of reviews have been published this year that cover the TROSY technique since its inception. ... 

So far, a large number of low-molar-mass systems have been studied by ultrafast fluorescence techniques in sub-nanosecond time regions [35-39]. Recently, a relatively slow (nanosecond) relaxation process proceeding in mixed low-molar-mass solvents, consisting in redistribution of components of the solvent mixture in the solvate shell of the fluorophore upon the excitation, has also been reported [40-43, 46, 47]. However, an important part of experimental studies is still concerned with relatively slowly relaxing biological systems, such as lipid membranes [48-50], proteins [51, 52], nucleic acids [53], and also colloidal [54] and polymer systems [55-57]. 

The difference between the chemical behavior of low-molecular compounds and highly ordered macromolecular systems (proteins, and nucleic acids) is a consequence of the fact that in the latter case the relaxation to the equilibrium state after local perturbation of each individual macromolecule can take a rather long time. Thus, a macromolecule ensemble can be considered as the mixture of nonequilibrium molecules. 

Geraldes CFGC, Luchinat C. Lanthanides as shift and relaxation agents in elucidating the structure of proteins and nucleic acids. Metal Ions in Biological Systems (Lanthanides and Their Interrelations with Biosystems). 2003 40 513-588. 

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