Conformational substates

Fernandez A 1990 Glassy kinetic barriers between conformational substates in RNA Phys. Reine Lett. 64 2328-233... 

Nadler and Schulten, 1984] Nadler, W., and Schulten, K. Theory of Mossbauer spectra of proteins fluctuating between conformational substates. Proc. Natl. Acad. Sci. USA. 81 (1984) 5719-5723... 

Figure 8 shows a one-dimensional sketch of a small fraction of that energy landscape (bold line) including one conformational substate (minimum) as well as, to the right, one out of the typically huge number of barriers separating this local minimum from other ones. Keeping this picture in mind the conformational dynamics of a protein can be characterized as jumps between these local minima. At the MD time scale below nanoseconds only very low barriers can be overcome, so that the studied protein remains in or close to its initial conformational substate and no predictions of slower conformational transitions can be made. 

Step 1 A short conventional MD simulation (typically extending over a few lOOps) is performed to generate an ensemble of protein structures x 6 71 (each described by N atomic positions), which characterizes the initial conformational substate. The 2-dimensional sketch in Fig. 9 shows such an ensemble as a cloud of dots, each dot x representing one snapshot of the protein. 

H. Grubmueller and P. Tavan. Molecular dynamics of conformational substates for a simplified protein model. J. Chem. Phys. 101 (1994)... 

Schamagl C, Raupp-Kossmann R, Fischer SF (1999) Molecular basis for pH sensitivity and proton transfer in green fluorescent protein protonation and conformational substates from electrostatic calculations. Biophys J 77 1839-1857... 

Hodel, A. Simonson, T. Fox, R.O. Brunger, A.T., Conformational substates and uncertainty in macromolecular free-energy calculations, J. Phys. Chem. 1993, 97, 3409-3417... 

This observation indicates that the multiple phases do not arise from static non-interconverting forms of the complex, and that they can best be interpreted by a kinetic scheme that involves dynamic conformational interconversion between conformational substates within state I. The analysis indicates that the... 

Fig. 21. (a) The local minima in a hypothetical conformational potential given by the solid line, with three conformational substates. The bottoms of the wells are parameterized by power laws, V, proportional to three values of a are shown in dashed lines, (b) The temperature dependence of the vibrational and collective motion x )c)... 

In physical terms the site inhomogeneous component may be conceived of either as slightly different protein binding sites for chromophores or as a distribution of protein conformational substates [127] at any one site. In operational terms the spectral forms are represented by the sub-bands of a gaussian or lorentzian decomposition analysis of absorption or fluorescence spectra. 

Frauenfelder, H., Parak, R, and Young, R. D. 1988. Conformational substates in proteins. Annu. Rev. Biophys. Biophys. Chem. 17 451-79. 

Ye, X., lonascu, D., Gruia, R, Yu, A., Benabbas, A., and Champion, P. M. 2007. Temperature-dependent heme kinetics with nonexponential binding and barrier relaxation in the absence of protein conformational substates. Proc. Nat. Acad. Sci. USA 104 14682-87. 

Miscellaneous bRC. - The bRC of R. sphaeroides contains one accessible cysteine at the H subunit (His H-156). Poluektov et al.m have bound a specific nitroxide spin label to this Cys and used temperature-dependent multifrequency (9 and 130 GHz) EPR to determine the motion of the protein. It was found that the restricted dynamics can be described as fast libration in a cone with a correlation time of >10 9 s. Several dynamically nonequivalent sites were observed that indicate conformational substates of local protein structure. 

One example of this possible existence of a hierarchy of receptor states has been discussed by Frauenfelder (1988). He reviewed studies on the binding of substrates and ligands to myoglobin. The process follows a power law, characterizing the protein as a complex system. Nuclear magnetic resonance (NMR) analyses revealed a number of conformational substates. 

Besides self trapping two alternative explanations, Fermi resonance and conformational substates, have been previously discussed as well [2]. In a recent study [6] we compared the 2D-IR spectrum of ACN with those of two molecular systems, which show the same splitting in the amide I band, and which were chosen as simple representatives of the alternative mechanisms. The three 2D-IR spectra differ completely, albeit in a well understood way. Based on the 2D-IR spectroscopic signature Fermi resonance and conformational sub-states can be definitely excluded as alternative explanations for the anomalous spectra of ACN. The 2D-IR spectrum of the amide I mode in ACN, on the other hand, can be naturally explained by self-trapping, as dicussed above. 

Conformational maps 60 Conformational substates in proteins 496 Conidia 20 Conjugate bases 486 Connective tissue 72, 431 Connexons 29... 

In summary then, over the past five years, since the last NMR chemical shift meeting in Maryland (57), progress with protein NMR shift (and EFG) calculations has been very exciting. At the time of the last US meeting, our view was that electric fields played a major role in the shielding differences seen due to folding for most nuclei. This now only seems likely for 19F in fluoroaromatic amino-acids and for the CO-heme conformational substates. This is particularly fortunate, however, since chemical shifts are now seen to be primarily probes of < >, / and %, the backbone and... 

Later the same groups extended studies of the role played by substrate in the formation and reactivity of hydroperoxo-intermediate in CYP101 by implementing labeled substrates and using 13C and 19F ENDOR for the detection of multiple conformational substates of the bound substrate.117 Two distances and two azimuthal angles (r = 4.5 A, 0 30°, and r = 4.8 A, 0 50°) have been resolved for the radius-... 

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