Conformational dynamics transitions

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. 

Weinan, E. Vanden-Eijnden, E., in Multiscale Modelling and Simulation, LNCSE 39, 2004 (chapter Metastability, conformation dynamics, and transition pathways in complex systems)... 

The tetrahydrodibenzo[6,/][l,4]diazocines (458) and the tetrahydrodibenzo[6,/]-[l,5]diazocines (459), which have two nitrogens in the heterocyclic ring, as well as their sulfur analogs (460) and (461) show conformational properties similar to those of the monoaza compound (456). Typical data are included in Table 3. The assignments of conformations and transition states for these dibenzo derivatives are supported by force-field calculations and by detailed dynamic NMR measurements <73JCS(Pl)205>. 

S S CONTENTS Preface, C. Allen Bush. Methods in Macromo-lecular Crystallography, Andrew J. Howard and Thomas L. Poulos. Circular Dichroism and Conformation of Unordered Polypeptides, Robert W. Woody. Luminescence Studies with Horse Liver Dehydrogenase Information on the Structure, Dynamics, Transitions and Interactions of this Enzyme, Maurice R. Eftink. Surface-Enhanced Resonance Raman Scattering (SERRS) Spectroscopy A Probe of Biomolecular Structure and Bonding at Surfaces, Therese M. Cotton, Jae-Ho Kim and Randall E. Holt. Three-Dimensional Conformations of Complex Carbohydrates, C. Allen Bush and Perse-veranda Cagas. Index. 

Multidimentional nonlinear infrared spectroscopy is used for identification of dynamic structures in liquids and conformational dynamics of molecules, peptides and, in principle, small proteins in solution (Asplund et al., 2000 and references herein). This spectroscopy incorporates the ability to control the responses of particular vibrational transitions depending on their couplings to one another. Two and three-pulse IR photon echo techniques were used to eliminate the inhomogeneous broadening in the IR spectrum. In the third-order IR echo methods, three phase-locked IR pulses with wave vectors kb k2, and k3 are focused on the sample at time intervals. The IR photon echo eventually emitted and the complex 2D IR spectrum is obtained with the use of Fourier transformation. The method was applied to the examination of vibrational properties of N-methyl acetamid and a dipeptide, acyl-proline-NH2.in D20. The 2D IR spectrum showed peaks at 1,610 and 1, 670 cm 1, the two frequencies ofthe acyl-proline dipeptide. Geometry and time-ordering of the incoming pulse sequence in fifth-order 2D spectroscopy is shown in Fig. 1.3. 

The latter point to a conformational transition of the protein at Tin. The time-resolved fluorescence studies indicated that the intrinsic Trp fluorescence emission of the protein was represented by a bimodal distribution with Lorential shape and was strongly affected by the protein conformational dynamics (Bismuto et al., 1999 D Auria et al.,1999). Parameters of the temperature dependence of the bimodal lifetime distribution, such as fraction relative intensity, the position of centres, and the distribution line widths,... 

Many bloactlve molecules are flexible, and their minimum energy conformation need not correspond to the receptor-bound conformation.7 Furthermore, conformational dynamics may be Important, with receptor molecule and substrate both changing conformation in order to elicit the biological response.5,30 In some cases, then, a system could show different pharmacophoric patterns for compounds which preferentially bind to the receptor s ground state, its activated state, and an intermediate state (transition state analogs).4... 

A further application of time-resolved fluorescence measurements is in the study of conformational dynamics of polymer chains in solution. Fluorescence anisotropy measurements of macromolecules incorporating suitable fluorescent probes can give details of chain mobility and polymer conformation (2,14). A particular example studied in this laboratory is the conformational changes which occur in aqueous solutions of polyelectrolytes as the solution pH is varied (15,16). Poly(methacrylic acid) (PMA) is known to exist in a compact hypercoiled conformation at low pH but undergoes a transition to a more extended conformation at a degree of neutralization (a) of 0.2 to 0.3 (1 6). Similar conformational transitions are known to occur in biopolymer systems and consequently there is considerable interest in understanding the nature of the structures present in model synthetic polyelectrolyte solutions. 

Recendy, Sneddon and Brooks (39), on the basis of their CHARMM simulations of conformational dynamics of Pro peptides in aqueous solution, have postulated involvement in electron transfer across the -(Pro) -bridge of P — a transitions at the i i angle, as the latter occur more rapidly and bring the donor-acceptor distance to a shorter range than the trans cis interconversion... 

Best RB, Chen YG, Hummer G. 2005. Slow protein conformational dynamics from multiple experimental structures The hehx/sheet transition of arc repressor. Structure 13 1755. 

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