Discrete conformations

The principle of the method is that once a substance crystallizes, the interconversion of the various conformers stops and so the crystals correspond to one discrete conformation or another. This has established, that 1,2-dichloroethane crystallises exclusively in the anti form, while ethylene chlorohydrin crystallizes in a gauche form because of intra molecular hydrogen bonding. But when the molecule crystallizes in two or more conformations, we say that it shows polymorphism. 

Another kind of stadc disorder which can exist in a protein crystal and which is different from a distribution of discrete conformations is lattice... 

The crystal structure of the cobalt-substituted enzyme was obtained with bicarbonate bound to the metal (Iverson et al. 2000). The structure shows Asn 202 and Gln75 hydrogen bonded to the metal-bound bicarbonate, suggestzing potential roles for these residues in either transition-state stabilization or orientation and polarization of CO2 for attack from the zinc-hydroxyl (Fig. 11.5). The crystal structure also shows three discrete conformations for Glu 84, suggesting a role for this residue in the transfer of protons out of the active site indeed, kinetic analyses of Glu 84 variants combined with chemical rescue experiments establish this residue as critical for proton transfer (Tripp and Ferry 2000). The location of Glu 62 adjacent to Glu 84 suggests a potential role in proton transfer as well. Although kinetic analyses of site-specific variants establish an essential role for Glu 62 in the CO2 hydration steps (Eqs. 11.3 and 11.4), the results were inconclusive regarding an additional role in proton transfer (Eqs. 11.5 and 11.6). 

For the cycloscan, conformational libraries are synthesized by cyclization of continuous or noncontinuous bioactive epitopes and not by their insertion into a scaffold. Originally, the concept of cycloscan was introduced for the generation of backbone-cyclized peptide libraries 467 however, cycloscan can also be applied to other modes of cyclization. In this approach all components of each sublibrary bear the identical sequence, and differ from each other in distinct parameters that affect their conformation, but do not alter their connectivity, and hence their potential bioactivity. This is achieved by gradually introducing discrete conformational perturbations, which allow an efficient screening of the conformational space of the parent peptide. The majority of the components of such libraries should be inactive, because they do not overlap the bioactive conformation. However, the peptide that does fit the bioactive conformation should be very potent and have all the pharmacological advantages of cyclic peptides. 

The tendency of proteins in biological systems to exist in a number of well-defined discrete conformational states sets the study of protein kinetics apart from the general theory of polymer physics, such as presented by Grosberg and Khokhlov [73], A rich theory of biological polymers, including of proteins and their conformational transitions, is presented in Cantor and Schimmel s Biophysical Chemistry [27],... 

Recently van Leeuwen reported the fiigt crystal structure of the diphosphite dicarbonyl rhodium catalyst HRh(CO)2(P P) [258]. Bomer et al. developed a new class of phosphonites which show promising results for the isomerization and subsequent hydroformylation of internal olefins [259]. The number of phosphite ligands based on supramolecular backbones such as calix[4]arenes is growing [260]. They are attractive because of their well defined structure combined with the ability to adopt several discrete conformations. Calix[4]arene diphosphites and calix[6]arene phosphites were first developed by BASF [261]. In... 

Equation (7.164) is the required relation between the solvation Helmholtz energy of the solute s and the solvation Helmholtz energies of the two con-formers A and B. Note that if qv and qe are the same for the two conformations, they will cancel in (7.165) and (7.163). What remains is only the rotational partition function of the two conformers. Generalization to the case with n discrete conformations is straightforward if there are n conformers, we have instead of (7.163) and (7.164)... 

G. M. Crippen. Prediction of protein folding from amino acid sequence over discrete conformation spaces. Biochemistry 30 4232-4237 (1990). 

The apparent reasons for this specificity need some amplification. An examination of the problem using Dreiding models reveals some interesting features for the approach of the olefin to the nucleophile. If there is a requirement for one carboxylate ion to be co-planar and therefore conjugated with the olefin then there are two discrete conformations to be achieved. Both can be realized but one of them is substantially more favorable than the other for the addition of the nucleophile. The two possibilities are depicted,... 

The physical properties of the ion channel protein suggested by the Markov model differ from the properties suggested by the fractal properties of the single-channel data. The Markov model suggests that (1) there are a few discrete conformational states corresponding to well-defined energy minima,... 

Apart from the rebuilding of the protein and the solvent model in the same way as it is done for structures at less than atomic resolution, the major part of manual modeling at atomic resolution concerns the introduction of multiple discrete conformations. Accurate modeling of multiple conformations, in particular in active sites, often leads to much cleaner electron density and increased interpretabiUty. 

Atoms with very elongated ellipsoids should be inspected. However, cases where it is appropriate to introduce two discrete conformations will usually be found when the residues mentioned in the list of disagreeable restraints are inspected. 

When a region of a structure with signs of multiple discrete conformations has been identified, the most efficient strategy for inclusion of such multiple conformations into the model is a stepwise procedure, in which changes in the parameterization are followed by some cycles of refinement. The principal steps are (see Figure 10.2) ... 

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