Alternating access model

The alternating access transport model has been used to describe the mechanism by which substrates are transported across the membrane via the monoamine transporters (Forrest et al., 2008). This model postulates that the transporter can exist in at least two conformations. These conformations include an extracellularly facing form that is open to the extracellular environment and can bind substrate and Na" and CF ions (Forrest et al., 2008). An intracellularly facing form allows the release of substrate into the cell and the binding of the countertransported ion to reverse the conformation of the transporter (Forrest et al., 2008). The alternating access model is supported by recent crystal structures of other transporters (Weyand et al., 2008 Faham et al., 2008). Two additional conformations of these transporters have also been described. A closed-closed conformation is predicted that prevents accessibility of substrate and ions from either side of the transporter. This closed-closed conformation was observed in the crystal structure of a leucine transporter... 

Consideration of relative proton affinities alone is not sufficient to explain the directionality of transport in proton pumps. For efficient proton pumping it is essential that the activated proton (state 2) cannot flow back to group A, which thermodynamically would be dictated by the fact that A has much higher proton affinity than C. To that effect, relative insulation to proton transport in state 2 is required either between B and A, or alternatively, between A and surface I. This requirement is often described in terms of an alternating access model [Jardetzky, 1966] and is now fairly well understood in bacteriorhodopsin [Lanyi, 1999]. Likewise, proton leakage from C to B must be prevented in step 4, where B has a much higher proton affinity than C. In the depicted scheme (Fig.2), the back flow of is hampered by the high proton activity of C relative to O, so that proton relay to B from A is rapid compared to alternative reprotonation from O via C. 

Eraly SA (2008) Implications of the alternating access model for organic anion transporter kinetics. J Membrane Biol 226 35-42. 

Fig. 4 Accessibility data on MsbA reveals the alternating-access mechanism, (a) Structural model of the open (provided by Chang) and closed states (PDB 3B60). The cytoplasmic region in the nitroxide scan (green) is highlighted, (b) Accessibility profile of the apo state. The cytoplasmic region shows high water accessibility, in line with the structure, (c) Plot of the water accessibility in water the structure, (d) Changes in water accessibility in the cytoplasmic region upon transition to the ADP-Vi intermediate, (e) Example of three saturation curves for a water-exposed side chain to extract the accessibility parameter. Adapted from [26]...

Alternatively, process models and the DCS can reside in an off-line personal computer, to provide a more portable, accessible, and maintainable dynamic representation of the plant. Such a virtual plant can be used to enhance process understanding and testing, investigate startups and transitions, diagnose and prevent abnormal operation, improve process automation, and prototype advanced control systems. 

The minimization of the model can proceed ad hoc guided by chemical intuition. Alternatively, minimal models may be derived by a well-defined coaise-graining transformation, beginning with an all-atom representation of the system. They may also be empirically derived by proposing a general functional form and performing a non-linear fit of the parameters of the function to a set of experimental data. These models are attractive in that the number of degrees of freedom and possible conformations is far fewer than the number of conformations accessible to an all-atom model. 

Most CVM computer codes are not necessarily optimized to work seamlessly with earthquake simulation codes. Modelers use additional tools to convert the data retrieved from a given CVM into grids or meshes. One particular tool of the sort is the unified community velocity model (UCVM) software framework (Small et al. 2015). UCVM is a collection of software tools developed and maintained by the Southern California Earthquake Center (SCEC) to provide an efficient and standard access to multiple, alternative velocity models. Although UCVM was primarily bruit to manage the SCEC community velocity models CVM-S and CVM-H for Southern California (Fig. 7), it supports and can be used to register other models as well. 

Because XPS is a surface sensitive technique, it recognizes how well particles are dispersed over a support. Figure 4.9 schematically shows two catalysts with the same quantity of supported particles but with different dispersions. When the particles are small, almost all atoms are at the surface, and the support is largely covered. In this case, XPS measures a high intensity Ip from the particles, but a relatively low intensity Is for the support. Consequently, the ratio Ip/Is is high. For poorly dispersed particles, Ip/Is is low. Thus, the XPS intensity ratio Ip/Is reflects the dispersion of a catalyst on the support. Several models have been reported that derive particle dispersions from XPS intensity ratios, frequently with success. Hence, XPS offers an alternative determination of dispersion for catalysts that are not accessible to investigation by the usual techniques used for particle size determination, such as electron microscopy and hydrogen chemisorption. 

An attractive alternative to these novel aminoalcohol type modifiers is the use of 1-(1-naphthyl)ethylamine (NEA, Fig. 5) and derivatives thereof as chiral modifiers [45-47]. Trace quantities of (R)- or (S)-l-(l-naphthyl)ethylamine induce up to 82% ee in the hydrogenation of ethyl pyruvate over Pt/alumina. Note that naphthylethylamine is only a precursor of the actual modifier, which is formed in situ by reductive alkylation of NEA with the reactant ethyl pyruvate. This transformation (Fig. 5), which proceeds via imine formation and subsequent reduction of the C=N bond, is highly diastereoselective (d.e. >95%). Reductive alkylation of NEA with different aldehydes or ketones provides easy access to a variety of related modifiers [47]. The enantioselection occurring with the modifiers derived from NEA could be rationalized with the same strategy of molecular modelling as demonstrated for the Pt-cinchona system. 

In 1995, one of the authors (A.K.) introduced the state of a molecule embedded in a perfect conductor as an alternative reference state, which is almost as clean and simple as the vacuum state. In this state the conductor screens all long-range Coulomb interactions by polarization charges on the molecular interaction surface. Thus, we have a different reference state of noninteracting molecules. This state may be considered as the North Pole of our globe. Due to its computational accessibility by quantum chemical calculations combined with the conductor-like screening model (COSMO) [21] we will denote this as the COSMO state. 

In the multimedia models used in this series of volumes, an air-water partition coefficient KAW or Henry s law constant (H) is required and is calculated from the ratio of the pure substance vapor pressure and aqueous solubility. This method is widely used for hydrophobic chemicals but is inappropriate for water-miscible chemicals for which no solubility can be measured. Examples are the lower alcohols, acids, amines and ketones. There are reported calculated or pseudo-solubilities that have been derived from QSPR correlations with molecular descriptors for alcohols, aldehydes and amines (by Leahy 1986 Kamlet et al. 1987, 1988 and Nirmalakhandan and Speece 1988a,b). The obvious option is to input the H or KAW directly. If the chemical s activity coefficient y in water is known, then H can be estimated as vwyP[>where vw is the molar volume of water and Pf is the liquid vapor pressure. Since H can be regarded as P[IC[, where Cjs is the solubility, it is apparent that (l/vwy) is a pseudo-solubility. Correlations and measurements of y are available in the physical-chemical literature. For example, if y is 5.0, the pseudo-solubility is 11100 mol/m3 since the molar volume of water vw is 18 x 10-6 m3/mol or 18 cm3/mol. Chemicals with y less than about 20 are usually miscible in water. If the liquid vapor pressure in this case is 1000 Pa, H will be 1000/11100 or 0.090 Pa m3/mol and KAW will be H/RT or 3.6 x 10 5 at 25°C. Alternatively, if H or KAW is known, C[ can be calculated. It is possible to apply existing models to hydrophilic chemicals if this pseudo-solubility is calculated from the activity coefficient or from a known H (i.e., Cjs, P[/H or P[ or KAW RT). This approach is used here. In the fugacity model illustrations all pseudo-solubilities are so designated and should not be regarded as real, experimentally accessible quantities. 

According to an early model.13 1 there are two adjacent accessible positions at the catalytic site, each favoring the coordination of the prochiral monomer with one of its two faces if the growing polymer chain alternates between the two positions at each insertion step, syndiotactic propagation is ensured. Due to the successive finding of a chain-end stereocontrol, this model has to be rejected. 

The kinetics of sorption can be considered as the sum of two processes 1) rapid sorption by labile sites which are in equilibrium with solutes dissolved in bulk solution, and 2) hindered sorption by sites which are accessible only by slow diffusion. Alternatively, sorption kinetics can be modeled by a radial diffu-sional process into spherical sorbents. The slow sorption process prevents complete equilibration within one day, the time used in typical batch experiments. Because the apparent rate of diffusion decreases with increasing hydrophobicity, time to equilibrium is longer for highly hydrophobic compounds. 

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