Physical labeling approach

Data on the intramolecular dynamics of proteins obtained by the physical labeling approach combined with other dynamical and complementary theoretical and experimental methods may be briefly summarized as follows. 

The basic idea underlying the physical labelling approach is the modification of the chosen sites of the object in question by specific compounds, which are boimd covalently (labels) and/or non-covalently (probes), whose properties make it possible to trace the state of the surrounding biological matrix by appropriate physical methods. The following main types of compounds are used as labels and probes to monitor the dynamic parameters of proteins (1) centers with unpaired electrons (stable nitroxide radicals, radical pairs and paramagnetic complexes) exhibit electron spin resonance (ESR), (2) luminescent fluorescence and phosphorescence chromophores, and (3) Mossbauer atoms (e.g. Pe) which gives the nuclear y-resonance (NGR) spectra. 

G. I. Likhtenstein, A. V. Kuiikov, A. I. Kotelnikov, and L. A. Levchenko, Methods of physical labels—a combined approach to the study of microstructure and dynamics in biological systems, J. Biochem. Biophys. Meth. 12, 1-28 (1986). 

From the late 1960 s to the early 1970 s, more direct approaches to the investigation of protein dynamics were intensively developed. Such investigations featured the application of physical methods, such as physical labeling, NMR, optical spectroscopy, fluorescence, differential scanning calorimetry, and X-ray and neutron scattering. The purposeful application of the approaches made it possible to obtain detailed information on the mobility of different parts of protein globules and to compare this mobility with both the functional characteristics and stability of proteins, and with results of the theoretical calculation of protein dynamics. 

The hazard classification should lead directly to labelling of acute health effects, environmental and physical hazards. The labelling approach that involves a risk assessment should only be applied to chronic health hazards, e.g. carcinogenicity, reproductive toxicity, or target organ systemic toxicity based on repeated exposure. The only chemicals it may be applied to are those in the consumer product setting where consumer exposures are generally limited in quantity and duration ... 

Once we have found a mixture or sublibrary that shows biological activity, how do we determine exactly which structure or stnictures are responsible for the activity We can purify and analyze as described in the previous section, but if no direct analysis is available, we need to encode or tag the support or the molecules themselves, using physical or molecular "barcodes." An obvious approach that can be used only with small libraries is to physically label each vial of one-bead one-compound resin. This may be practical for a few tens of compounds, but what if we have a library of 32,(X)0 compounds, or even 1.000,000 compounds, in a mixture Clearly, there is a need for a more automated means of identifying the. structures that arc in the library. 

Fig. 32. NSE spectra of labelled cross-links in a four-functional PDMS network at four different Q-values. Included is a common fit with Eq. (63). The shaded area displays the time independent EISF part in the spectra. Note that the spectra do not approach 1 for t 0. This is related to a fast relaxation process of the deuterated network strands which has not been substracted. (Reprinted with permission from [84]. Copyright 1988 The American Physical Society, Maryland)...

Fig. 6.8 Q dependence of the two eigenvalues Ai(Q) solid line) and A2(Q) dotted line) predicted by a two-component dynamic RPA approach for the case of an hA-dB labelled diblock copolymer melt. Calculations were performed with/=0.5, Rg =Rg =40 A, Na=Ny=200, Ku=0, Ai(Q) describes the collective mode of the diblock copolymer chains. The Rouse rates were taken from PE and PEE at 473 K (see Table 6.2). (Reprinted with permission from [44]. Copyright 1999 American Institute of Physics)...

The first class of approaches could be labelled as exact . A complete diagonalization of the full static electrons + ions hamiltonian in principle allows to access any dynamical process. It should thus provide a fully detailed description of the dynamics of the system. However, up to now, such calculations have focused on structural properties rather than on dynamical ones. Furthemore, even today s computer capabilities barely allow such calculations for clusters of more than very few atoms [14]. Cluster s size limitations are comparable for molecular physics s technics, based on the time propagation of quantal wavepackets [15]. These exact approaches hence mainly provide benchmarks for the other theories, but do not really allow a full exploration of the various facets of the physics involved. 

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