Orientational constraints

In the case of the retro Diels-Alder reaction, the nature of the activated complex plays a key role. In the activation process of this transformation, the reaction centre undergoes changes, mainly in the electron distributions, that cause a lowering of the chemical potential of the surrounding water molecules. Most likely, the latter is a consequence of an increased interaction between the reaction centre and the water molecules. Since the enforced hydrophobic effect is entropic in origin, this implies that the orientational constraints of the water molecules in the hydrophobic hydration shell are relieved in the activation process. Hence, it almost seems as if in the activated complex, the hydrocarbon part of the reaction centre is involved in hydrogen bonding interactions. Note that the... 

Several local labels need to be measured, usually one-by-one in individual samples in the case of 19F-NMR. The combined set of anisotropic NMR parameters then allows one to re-construct the geometry of the entire peptide and to determine its alignment in the membrane, as illustrated in Fig. 1 [35-37, 47, 48]. The only prerequisite is that the 19F-labelled moiety has to be rigidly attached to the peptide backbone, and that the peptide assumes a well-defined secondary structure. Provided that a sufficient number of local orientational constraints can be measured... 

The diffusion constant D with the underlying microviscosity , and the two order parameters , <(P4> reflecting the degree of orientational constraint have been successfully determined from the fluorescence anisotropy decay in... 

The motional characteristics of interest are typically those governed by the phospholipid fatty acyl chains and head-group region and the neutral lipid or protein components of membranes. Rotational motion can be subdivided into a structural component, the order or degree of orientational constraint,... 

The observation that r(t) decays to the finite value rro soon led to the recognition that the fluorophore DPH has an orientational motion which is restricted due to the surrounding lipid chains/35-37 From this the wobbling-in-cone model(37 43 44) was developed. In this model, DPH was assumed to wobble within a cone of half angle 6C (which relates to the degree of orientational constraint, order, or rm) with a wobbling diffusion constant D (which relates to the rate of motion) with... 

Fig. 8 Proposed model for gramicidin S in a membrane according to the orientational constraints obtained from and N-NMR. The upright backbone alignment (r 80°) and slant of the /3-sheets (p -45°) are compatible with the formation of an oligomeric /3-barrel that is stabilized by hydrogen bonds (dotted lines). A The oligomer is depicted sideways from within the lipid bilayer interior (showing only backbone atoms for clarity, but with hydrophobic side chains added to one of the monomers). Atomic coordinates of GS were taken from a monomeric structure [4], and the two DMPC lipid molecules are drawn to scale (from a molecular dynamics simulation coordinate file). The bilayer cross-section is coloured yellow in its hydrophobic core, red in the amphiphilic regions, and light blue near the aqueous surface. B Illustrates a top view of the putative pore, although the number of monomers remains speculative...

Schmitz, K. S., and Schurr, M. j. (1972). The role of orientation constraints and rotational diffusion in bimolecular solution kinetics. J. Phys. Chem. 76, 534-545. 

Aromatic features can be modeled as layer 4 point features or as layer 3 features. In Catalyst, Phase, and LigandScout these features are also attributed with a ring plane normal defining the spatial orientation (layer 3 feature). In MOE, the selected pharmacophore scheme determines whether a ring plane orientation constraint is included or if aromaticity is modeled as a pure point feature with a tolerance sphere. 

Ketchem RR, Lee KC, Huo S, Cross TA. Macromolecular structural elucidation with sohd-state NMR-derived orientational constraints. J. Biomol. NMR. 1996 8 1-14. 

Consider a given molecular contour surface G(a). If the size s of the cubes is chosen small enough, then any finite polycube P can fit within G(a). As in the two-dimensional case, we do not consider orientation constraints and we assume that the contour surface G(a) and polycube P may be translated and rotated with respect to one another the relative orientation of G(a) and the cubic grid is not fixed. In this model, the identity of a polycube is independent of its orientation. Two polycubes P and F are regarded identical if and only if they can be superimposed on one another by translation and rotation in 3D space. Note, however, that the polycube method of shape analysis and determination of resolution based similarity measures can be augmented with orientation constraints, suitable for the study of molecular recognition and shape problems in external fields or within enzyme cavities [240,243]. 

This section briefly describes the 19F NMR experiments performed on 19F-labeled peptides, the fundamental NMR parameters that are used to obtain orientational constraints, and the means by which peptide structure is determined from these constraints. 

Using a number of orientational constraints from NMR measurements, the orientation of the peptide in the membrane can be determined, assuming that the structure of the peptide is known. The peptides we have studied mostly have well defined structures, such as a-helices or rigid cyclic conformations. The validity of the proposed peptide structure as it interacts with the membrane can also be tested using the fit of the data [45, 49], For example, the data can be fitted to different helical models, such as a- and 3i0-helix a good... 

To obtain orientational constraints, peptide/lipid samples for 19F NMR studies are usually prepared with lipid bilayers that are macroscopically oriented on glass plates [52-54], Lipids and peptides in appropriate amounts are co-dissolved in organic solvent and spread onto thin glass plates. After removal of the solvent, the plates are stacked and placed in a... 

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