Conformational uniqueness

Unlike desferrioxamine analogs designed for specific therapeutic purposes described above, chiral DFO analogs that form conformationally unique complexes with iron(lll) were designed to serve as chemical probes of microbial iron(lll) uptake processes. As mentioned above, ferrioxamine B can form a total of five isomers when binding trivalent metal ions, each as a racemic mixture. Muller and Raymond studied three separate, kinetically inert chromium complexes of desferrioxamine B (N-cis,cis, C-cis,cis and trans isomers), which showed the same inhibition of Fe-ferrioxamine B uptake by Streptomyces pilosus. This result may indicate either that (i) ferrioxamine B receptor in this microorganism does not discriminate between geometrical isomers, or that (ii) ferrioxamine B complexes are conformationally poorly defined and are not optimal to serve as probes. 

In Scheme 25, the conformations of scaffolds (1) and (4) from Scheme 24 are depicted for ring structures consisting of L-Ala and one D-Ala as models. In both cases the D-Ala residue (and in the same manner other D-amino acid or structure-inducing residues) occupy the i+1 position in the (3-turn thus forcing each position in the scaffolds to be conformationally unique and defined. 

Lionheart, W.R.B., 1997. Conformal uniqueness results in anisotropic electrical impedance imaging. Inverse Probl. 13 (1), 125-134. 

Conformational uniqueness, also referred to as conformational specificity, is defined as the preference for one conformation, usually the native structure, over all others. It has been suggested that conformational specificity is imparted through constraints imposed by a large number of individually small interactions distributed throughout the polypeptide, which arise from the interplay between parameters such as the shape and polarity of the side chains and the backbone conformation. ... 

After an initial starting geometry has been generated and optimized (e.g., in a force field), the new conformation is compared with all the previously generated conformations, which are usually stored as a list of unique conformations. If a substantially different geometry is detected it is added to the list otherwise, it is rejected. Then a new initial structure is generated for the next iteration. Finally, a preset stop criterion, e.g., that a given number of loops has been performed or that no new conformations can be found, terminates the procedure. 

Dmparison of various methods for searching conformational space has been performed cycloheptadecane (C17H34) [Saunders et al. 1990]. The methods compared were the ematic search, random search (both Cartesian and torsional), distance geometry and ecular dynamics. The number of unique minimum energy conformations found with 1 method within 3 kcal/mol of the global minimum after 30 days of computer processing e determined (the study was performed in 1990 on what would now be considered a / slow computer). The results are shown in Table 9.1. 

For a conformation in a relatively deep local minimum, a room temperature molecular dynamics simulation may not overcome the barrier and search other regions of conformational space in reasonable computing time. To overcome barriers, many conformational searches use elevated temperatures (600-1200 K) at constant energy. To search conformational space adequately, run simulations of 0.5-1.0 ps each at high temperature and save the molecular structures after each simulation. Alternatively, take a snapshot of a simulation at about one picosecond intervals to store the structure. Run a geometry optimization on each structure and compare structures to determine unique low-energy conformations. 

If the sampling interval is too short, the total number of structures that belong to unique structural families is small compared to the total number available. If the sampling interval is too large, the total number of available structures is small, and you can miss unique conformations. 

Shielding and Stabilization. Inclusion compounds may be used as sources and reservoirs of unstable species. The inner phases of inclusion compounds uniquely constrain guest movements, provide a medium for reactions, and shelter molecules that self-destmct in the bulk phase or transform and react under atmospheric conditions. Clathrate hosts have been shown to stabiLhe molecules in unusual conformations that can only be obtained in the host lattice (138) and to stabiLhe free radicals (139) and other reactive species (1) similar to the use of matrix isolation techniques. Inclusion compounds do, however, have the great advantage that they can be used over a relatively wide temperature range. Cyclobutadiene, pursued for over a century has been generated photochemicaHy inside a carcerand container (see (17) Fig. 5) where it is protected from dimerization and from reactants by its surrounding shell (140). 

A database management system (DBMS) is used by most LIMS systems for storing data. Examples of commercially available DBMS are DB2, DBASE, Informix, INGRES, ORACLE, and RDB. AH of these DBMS conform to the "relational" model developed by Codd (19). Eigure 3 demonstrates the use of a relational DBMS for storing LIMS data. Here data is grouped by type so customer and analysis requests are stored separately from sets of sample information which are, in turn, stored separately from sets of analysis results. Individual records are linked or related by unique identification data. 

For any given protein, the number of possible conformations that it could adopt is astronomical. Yet each protein folds into a unique stmcture totally deterrnined by its sequence. The basic assumption is that the protein is at a free energy minimum however, calometric studies have shown that a native protein is more stable than its unfolded state by only 20—80 kj/mol (5—20 kcal/mol) (5). This small difference can be accounted for by the favorable... 

Hydantocidin. Hydantocidin (182), C2H2QN2O3, is elaborated by S. hygroscopicus (278). It is unique in that the anomeric carbon of the ribosyl moiety forms the spHo bond of hydantoin (279). The ribofuranose moiety which has been reported to be in a Q -endo conformation (279) has been synthesized (280,281). Hydantocidin is a herbicidal nucleoside with activity against monocotyledenous and dicotyledenous plants. 

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