Conformational dynamics model

For dynamical studies of diffusion, conformational and transport behavior under shear stress, or kinetics of relaxation, one resorts to dynamic models [54,58,65] in which the topological connectivity of the chains is maintained during the simulation. 

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

In order to exemplify how the various computed indices can be used in testing the predictions of OEMO theory within the framework of the dynamic model we shall consider once again the problems of conformational isomerism of 1,3-butadiene and geometrical isomerism of 1,2-difluoroethylene. We first consider the cis and tram conformers of 1,3 butadiene. 

The observed conformational states and dynamical properties of TGF-b ligands suggest a dynamical model of their cooperative interaction with recep-... 

Chodera, J.D., Singhal, N., Pande, V.S., Dill, K.A., Swope, W.C. Automatic discovery of metastable states for the construction of Markov models of macromolecular conformational dynamics. J. Chem. Phys. 2007, 126, 155101-17. 

Vgand Z, parameters from a joint ED, MW and ab initio analysis for the so-called dynamic model. Mean values for the two conformers present in the vapor. rr (C2—C3), opposite to the COOH group(s). rfMean values. 

It is generally recognized that in order to analyze the stereochemical features of real systems (molecules, or groups of molecules and reactions) it is useful to abstract those features which determine the properties of interest and to represent them in terms of a single model system. It is possible to perform an isomorphic mapping of the essential stereochemical features of each of the real systems onto this model, and an equivalence relation will thus exist between the real systems. We shall say that any two systems whose static stereochemistry (structure, conformation) and conformational dynamics may be represented by the same abstract model exhibit stereochemical correspondence. 

The use of 19F NMR for a variable temperature (VT) NMR study of fluorinated taxoids is obviously advantageous over the use of H NMR because of the wide dispersion of the l9F chemical shifts that allows fast dynamic processes to be frozen out. Accordingly, F2-paclitaxel 65 and F-docetaxel 66 were selected as probes for the study of the solution structures and dynamic behavior of paclitaxel and docetaxel, respectively, in protic and aprotic solvent systems.77 The inactive 2, 10-diacetyldocetaxel (73) was also prepared to investigate the role of the 2 -hydroxyl moiety in the conformational dynamics.89 While molecular modeling and NMR analyses (at room temperature) of 73 indicate that there is no significant conformational changes as compared to paclitaxel, the 19F NMR VT study clearly indicates that this modification exerts marked effects on the dynamic behavior of the molecule.77... 

The value of ( used here corresponds to 10 3 of its value in room temperature aqueous solutions. [80] On the one hand, using such weak friction improves the sampling efficiency in the simulations and does not affect equilibrium structural properties. On the other hand, the dynamical properties that we observe may be different from those probed by SM-FRET techniques, which would not be able to resolve conformational dynamics on such fast time scales. Thus, the relevance of the following analysis of dynamical properties relies on the assumption that increasing the friction will not significantly alter our main conclusions. It is interesting to note in this context that the folding mechanism in similar models has been observed to be relatively insensitive to the value of the friction coefficient. [81]... 

Unfolded state (3 is characterized by a wide uni-modal and symmetrical distribution of the end-to-end distance. The distribution narrows down in a uniform manner with increasing Tw Thus, in the case of unfolded state / , one does not observe a correlation between R and the time scale of conformational dynamics. This behavior is similar to that previously observed in the case of a free-jointed homopolymer model. [54]... 

It is also of interest to compare our results with experiment. The experimental study most closely related to the model considered here is the SM-FRET assay by Hochstrasser and co-workers on the disulfide cross-linked two-stranded coiled-coil from the yeast transcription factor GCN4. [30,33] Our results appear to be consistent with many of the experimental observations reported in Refs. [30,33], For example, surface-immobilization in the folded state has a rather small effect on the R distribution, the folded and unfolded states are seen to correspond to narrow and broad R distributions, respectively, and conformational dynamics is seen to be characterized by a wide dynamical range in the midpoint and unfolded states. Our analysis can also help in the interpretation of the experimental results. For example, surface-... 

Calculations at the MP2/6-31G07) level have indicated that planar and nonplanar conformers of thioxanthone differ in energy by less than 1 kcalmol-1 the dihedral angle of the latter is 173.3°. Computed and experimental ionization potentials and absorption spectra suggest contributions from both conformers and a dynamic model involving a butterfly-like motion is proposed <2006JPH(179)298>. 

Ligand Solution conformation Charge/tautomeric state Solution dynamics Bound conformation Pharmacophore models 1D/2D NMR Chemical shift Line shape/relaxation analysis TrNOE All of the above, including 1D/2D of multiple ligands... 

Information Ligand conformation Pharmocophore model Bound ligand conformation Binding site/ orientation 3D structures Dynamics... 

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