Representation molecular structure conformation

Fig. 4. The molecular structure, determined by solution NMR (James et al., 1997), of Syrian hamster 90-231 (SHa90-231) prion with ball-and-stick representation of the HI domain (SHal09-122 MKHMAGAAAAGAW). Note that two short /(-chains (SI, S2) nearly stack in the hydrogen-bonding direction. If the palindromic polyalanine region was also in a /(-conformation, there would be a three-stranded /(-sheet. The structural difference between PrPc and PrPSc is in the 90-145 domain. [Model drawn using MOLSCRIPT (Kraulis, 1991)].

FIGURE 5.26 (See color insert following page 280.) A representation of the slot model illustrating potential constrained-shape solute (BaP) interactions with the conformational ordered cavities of a polymeric Cjg stationary-phase simulation model. Also included on the chromatographic surface is an identical-scale molecular structure of 1,2 3,4 5,6 7,8-tetrabenzonaphthalene (TBN). 

Figure 10 Molecular structure of 2a and crystal packing of (a) the chiral inclusion crystal 2a (- )4 and (b) the chiral crystal of 2a on its own. (c) Space-filling representation of molecular structure of 2a as found in the two crystal structures. Conformations are similar in the two cases.

FIGURE 5 Left Schematic representation of the ternary complex of y-cyclodextrin prior to the addition reaction. Right Molecular structure of the product benzoin in an extended conformation (27). 

Figure 3. Molecular structure of a propoxycalix[4]arene in the cone conformation and a schematic representation of the four possible calix[4]arene conformations. A, electron-accepting group.

The 3-dimensional molecular models of the avermectins helped us to define the subtle structural differences recognized by the MAbs, but these models must be viewed and interpreted with caution. Since we could not invoke solvent interactions, we have no way to know what the differences may be between these gas-phase representations and the conformations assumed in solution. On the other hand, data for other hydrophobic compounds, including some macrolide antibiotics, suggests that their gas-phase and solution structures are very similar, and the major differences we observed in Figure 4 were in hydrophobic parts of the molecule. For this reason, we did not attempt to model the last analog in Table I, the 4" deoxy-4"epimethylamino avermectin Bi hydrochloride, even though it was the best competitor in the EIAs, because it is far more water soluble than the others. Another concern is that the samples compared in the competition EIAs were mixtures of isomers, e.g., abamectin is actually avermectin Bia Bib 80 20. Because it is virtually impossible to obtain the purified individual isomers for the EIA or other tests of antibody specificity, we can only assume that the competition EIA results primarily reflected how each MAb bound to the maior isomer. 

In contrast to topological approaches, methods based on geometrical representations of molecular structures can be used instead. Among them, flexible superimposition of molecules onto one or multiple conformations of a reference bioactive ligand is a well-established methodology... 

Fig. 8.5 Molecular structures of a urea peptide (A) in the crystal state (B, ORTEP representation with ellipsoids shown at the 40% probability level) and in a CDCI3 solution (MM2 energy-minimized conformation) [38].

The drawing of a molecular structure will show all the bond connectivities between neighbouring atoms and, if a stereochemistry representation is used, the configuration and the conformation of the molecule. The NMR experiment is based on the detection of spin systems and consequently the molecular structure can be defined in terms of spin systems using chemical shifts, coupling networks and, for stereochemical information, the relaxation times of the NMR active nuclei. 

Many other intermolecular and intramolecular contacts are described by distances (hydrogen bond lengths, van der Waals contact, experimentally determined distances from nuclear Overhauser effect (NOE) spectra, fluorescence energy transfer, etc.) so that the distance matrix representation can be used to specify all the known information about a molecular structure. These bounds are entered into a distance geometry program, as are other bounds that specify constraints on modeling problems, such as constraints to superimpose atoms in different molecules. Hypotheses about intra- or intermolecular conformations and interactions are easily specified with distance constraints models can be built quickly to test different hypotheses simply by changing the distance constraints. 

Membrane environment. Membranes are large structures, translocation of molecular structures through membranes may involve significant conformational changes, and so these systems are natural candidates for implicit solvent modeling. One of the challenges here is accurate and computationally facile representation of the complex dielectric environment that, in the case of membranes, includes solvent, solute, and the membrane, all with different dielectric properties. Corrections to the GB model have been introduced [45-47] to account for the effects of variable dielectric environment. Other implicit membrane models, not based on the GB, have also been proposed [48]. 

Most researchers find it useful to employ three-dimensional graphics representations of peptides and proposed mimetics in their studies. This rudimentary level of molecular modeling allows for manipulation and geometric comparison of complex molecular structures. Using standard molecular bonding parameters, this level of analysis can test whether the proposed mimetic has the possibility of adopting the desired conformation, so that it can present important molecular recognition features in the appropriate orientation. 

Figure 5.6. Description of the molecular structure of the parent model protein (GVGVP) , which should be recognized as equivalent to (VPGVG) . (A) A series of P-turns involving residues VPGV. (B) The P-turn obtained from the crystal structure of the cyclic conformational correlate cyclo(GVGVP)3 shown in Figure 5.4B. (C,D) Schematic helical representations without P-turns (in C) and showing p-turns as spacers between turns of a helix, called the P-spiral. (E) Cross-eye stereo view of the poly(GVGVP) p-spiral in side view below and in axis view above. (F) Cross-eye stereo view of the twisted filament composed of three P-spirals. Before passing...

Fig. 23 Molecular structures of drug conjugate 122 and representation of its conformational changes upon pH variation from 7.4 to 6.8...

FIGURE 2.8 (a) Molecular structure of 10 and (b) schematic representation of reversible transformation of helical coils and straight rods of 10 and (c) molecular modeling of 10 indicating that boat conformations of macrocycles stabilize the helical coil structure top view (left) and side view (right). Reprinted with permission from Reference 62. Copyright 2009 American Chemical Society. For a color version of this figure, see the color plate section. 

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