Structural hypotheses

The absence of a high-resolution structure of any transporter in the NT family greatly complicates the interpretation of structure-function studies. The recent identification of the bacterial and archaeal transporters and their potential suitability for direct structural studies raises the exciting prospect of being able to test specific structural hypotheses related to transport. In the meantime, the use of the numbering scheme introduced here in a context of predicted structural properties should facilitate communication among researchers on different members of the transporter family as the mechanistic details are being probed. 

Reviews on water structure models include Mishima and Stanley (1998), Wallqvist and Mountain (1999), and Ludwig (2001). Mishima and Stanley (1998) concentrated their review on three relatively recent water structure hypotheses (1) the stability limit hypothesis (Speedy, 1982), (2) the singularity-free hypothesis (Sastry et al., 1996), and (3) the liquid-liquid phase transition hypothesis (Poole et al., 1992). 

We have constructed the several structural hypotheses mentioned above so as to be in agreement with available experimental data (or at least our interpretation of them). Testing of these hypotheses requires new experimental data (see Section VII). For the present we turn to an examination of the consistency of the ideas advanced. 

E. Torrens (2003). Structural, chemical topological, electrotopological and electronic structure hypotheses. Comb. Chem. HTS 6 801-809. 

A hypothesis picture of hydrate growth at a crystal is shown in Figure 3.21, modified from Elwell and Scheel (1975). This conceptual picture for crystal growth may be combined with either the labile cluster or local structuring hypotheses for nucleation. 

Jain, A. N. ligand-based Structural Hypotheses for Virtual Screening. J. Med Chem. 2004, 47, 947-61. 

He proposed to consider, without resorting to any structural) hypotheses , the first product of benzene substitution in the order of both the direct and th r -... 

Until the 1980s, the major methods of investigation in ionics were nonspec-troscopic. For example, conductance results were used to infer the existence of complex ions. Alternatively and typically, the change of the dielectric constant of a solution as a function of the concentration of ions (measurements at various frequencies) was interpreted in terms of structural hypotheses about ion-solvent interactions. 

As indicated in Sections 3 and 4, exciton analysis of spectra is a potentially useful way of interpreting the spectra, understanding (B)Chl-(B)Chl interactions, and possibly verifying structural hypotheses. One also sees that it is not without controversial aspects, although as long as structural information is incomplete one is still free to assume structural features that suit the exciton analysis and thereby minimize controversy. The situation is quite different when detailed knowledge of structure is available, i.e., in practice when a structural model based on X-ray diffraction at or near atomic resolution has been established. This is the situation to be considered in the remainder of this chapter. 

MS/MS fragmentation behavior of the impurities yields no definitive structural hypotheses. 

Polypeptide molecules of course exhibit many more vibrational frequencies than the half-dozen or so amide modes. For example, a molecule as simple as the extended form of polyglycine has about 50 bands in its IR and Raman spectra. It is clear that the information contained in the entire spectrum must therefore be a more sensitive indicator of three-dimensional structure. The only way to utilize this information fully is through a normal-mode analysis, that is, by comparing observed frequencies with those calculated for specific secondary structures. This can provide a powerful method for testing structural hypotheses in great detail. 

Further information can be gained by site-directed mutagenesis. Functional changes in response to changes of amino acids thought to be involved in binding or in the catalytic mechanism allow the validatation of structural hypotheses [31-33]... 

Fig. 1.22. Structure hypothesized for the coordination polymer formed by [Cu(Bpph 4CN)2] with Rh2(CF3COO)4.

There are three caveats when one forms structural hypotheses on the basis of the observed CIDNP signals. First, the polarization intensity of a residue is not simply a constant that is specific for that particular amino acid but is subject to a Stem-Volmer competition of all accessible residues for the excited dye molecules, so CIDNP of an accessible amino acid can be suppressed by other accessible amino acids that are more reactive that problem is most pronounced for histidine. Second, in one study surface accessibility as detected by CIDNP was found to depend not only on the location of the amino acid but also to some extent on the nature of the dye " no systematic investigation of this effect with a range of known protein structures has yet been attempted. Third, the radical cation of a tr)q3tophan or tyrosine residue could undergo electron transfer with a nearby tyrosine or tr)q)tophan that is located in the interior of the protein. If this pair substitution causes polarizations of the inner residue to develop, misinterpretations as to the protein structure might obviously result. This problem has attracted considerable attention. ° For lysozyme, such an intramolecular electron transfer appears to be more important in the denatured state than in the native state. ... 

These four basic hypotheses can themselves, like the structural hypotheses of chirality, be grouped into de facto selection hypotheses (1) and (2) one could also use here the term spontaneous, depending on whether one has a quantum or classical picture of the process and the two de lege selection hypotheses (3) and (4). 

Bernard DP, Hunsaker DB Jr, Marmorek DR (1993) Tools for improving predictive capabilities of environmental impact assessments Structured hypotheses, audits and monitoring. In Hildebrand SG, Cannon JB (eds) Environmental analysis The NEPA experience. Lewis, Boca Raton, Florida, pp 547-564... 

Jain AN. Ligand-based structural hypotheses for virtual screening. J Med Chem 2004 47(4) 947-961. 

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