Molecular flexibility and

Lu JJ, Crimin K, Goodwin JT, et al. (2004) Influence of molecular flexibility and polar surface area metrics on oral bioavailability in the rat. /. Med. Chem. 47 6104-6107. 

Of great interest to the molecular biologist is the relationship of protein form to function. Recent years have shown that although structural information is necessary, some appreciation of the molecular flexibility and dynamics is essential. Classically this information has been derived from the crystallographic atomic thermal parameters and more recently from molecular dynamics simulations (see for example McCammon 1984) which yield independent atomic trajectories. A diaracteristic feature of protein crystals, however, is that their diffraction patterns extend to quite limited resolution even employing SR. This lack of resolution is especially apparent in medium to large proteins where diffraction data may extend to only 2 A or worse, thus limiting any analysis of the protein conformational flexibility from refined atomic thermal parameters. It is precisely these crystals where flexibility is likely to be important in the protein function. 

Positioning all electrophilic functional groups in the middle of the molecule with none at any terminal positions will reduce molecular flexibility and accessibility of the electrophilic functional group(s) to interact with cellular nucleophiles such as DNA. 

The effects of limited molecular flexibility and increasing deviation from coplanarity of the anthracene and ethylene ir-systems on the radiative properties have been assessed in a series of symmetrically 2,2-substituted l-(9-anthryl)ethylenes 87 [63]. As for structurally rigid 9-anthrylethylenes 88 and 89, for which rotation about the anthryl-ethylene single bond is not possible, and in which the ethylene double bond has been forced to be coplanar with the anthracene -system, their fluorescence quantum yields in cyclohexane are exceptionally high, i.e., 0.94 and 0.96, respectively, and the Stokes shifts are less than 200 cm 1 (see Figure 15). For nonplanar 9-vinylanthracene 87a and its dimethyl derivative 87b, whose ethylene double bond may be twisted out of the plane of the anthracene by about 60°, the quantum yield is 0.63, and the Stokes shifts are around 1000cm-1 (see Table 16). 

The separation nf the poly saccharide components utilizes their different solubilities, polar groups, extents of branching, molecular weights, and molecular flexibilities and may he accomplished batebwisc or with easily automated column techniques such as column ur high performance liquid chromatography. These pmcedures have been summarized in several reviews. 

One group of polyphosphazenes has received considerable attention because of their advantages for lithium ion conduction. These are polyphosphazenes with oligo-ethyleneoxy side groups. They are characterized by their high molecular flexibility and their ability to coordinate weakly to lithium and other monovalent ions. A well-known example is poly[to(methoxyethoxyethoxy)phosphazene) (3.79), also known by the acronym MEEP (MethoxyEthoxyEthoxyPhosphazene). Numerous other polyphosphazenes with different alkyl ether side groups and different architectures have also been studied as ionic conductors. 

By lowering the temperature, it is often possible to slow down the rate of intramolecular processes of this kind, and hence to obtain NMR spectra consistent with expectation. It is then possible to measure the rate constant for the process, and hence the activation barrier. In the case of PF5, this barrier amounts to 18 kJ mol-1. This kind of experiment gives much useful information about molecular flexibility, and about the relative energies of isomers. 

HY) as possible features. Two additional constraints were set (i) because of the molecular flexibility and functional complexity of the training set, only pharmacophores containing five features should be considered and (ii) the program was forced to include a positive ionizable feature in the composition of hypotheses, on the basis of the literature reporting a basic atom (usually a nitrogen) as a critical structural determinant for arAR antagonistic activity. 

For synthetic polymers composed of 4-hydroxylphenyl, guaiacyl, and syringyl units and for polyurethanes containing lignin, the Tg values are affected by factors such as structure, molecular flexibility, and molecular weight of the other components of the polymers (Hatakeyama and Kanetsuna 1989, Yoshida et al. 1990). 

Very rigid macromolecules are at the opposite end of the spectrum of properties from elastomers, which are characterized by weak intermolecular forces, a high degree of molecular flexibility, and an absence of regular intermolecular order. 

Comparisons of the Doi-Edwards (DE) theory for semidilute solutions of rods with experiments are complicated by the lack of ideality of most rod-like molecules. The behavior is sensitive to molecular flexibility and polydispersity, which are difficult to avoid in such solutions. Because the rotary diffusivity of a rod has such a strong dependence on the molecular weight M of the rod, scaling as in semidilute solution, the effects of... 

Mekenyan O, Dimitrov S, Serafimova R, Thompson E, Kotov S, et al. Identification of the structural requirements for mutagenicity by incorporating molecular flexibility and metabolic activation of chemicals I TA100 model. Chem Res Toxicol 2004 17(6) 753-66. 

Fisher CL, Tainer JA, Pique ME, Getzoff ED. Visualization of molecular flexibility and its effects on electrostatic recognition. J Mol Graph 1990 8 125-145. 

The kinetics of protein adsorption at an interface can be measured by monitoring surface concentration and surface pressure i.e. depression of surface tension (V) as a function of time (3/7). -casein is more surface active than serum albumin or b-Lg and much more so than lysozyme. This reflects not only the rate of diffusion of the native protein to the interface, but also its molecular flexibility and amphipathic nature (15,17,22). 

G. A. Arteca,/. Comput. Chem., 14, 718 (1993). Global Measure of Molecular Flexibility and Shape Fluctuations About Conformational Minima. 

The spin-labeled cardiolipin molecule is a phospholipid, containing a polar "head" group and four fatty acid hydrophobic "tails". It has been incorporated into lipid bilayers as a probe of molecular flexibility and mobility in model membranes.24... 

Ishihara developed a highly diastereo- and enantioselective direct Man-nich-type reaction of aldimines with 1,3-dicarbonyl compounds using chiral lithium binaphtholate salts as effective Lewis-acid-Bronsted-base catalysts (Scheme 2.5). ° The stereoselectivity of the Mannich products anti-S and syn-7 ) was reversed when the nucleophile was changed from acyclic 1,3-dicarbonyl compound 4 to cyclic compound 6. The molecular flexibility and acidity of the nucleophiles 4 and 6 would be the major factor in differentiating the two reaction pathways. 

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