Carbohydrate modeling, problems

The rings in sugars pose a particular problem to general-purpose force fields and should be modeled using a force field designed specifically for carbohydrates. 

The binding specificity of d-[ C]glucose by the taste-papillae membranes, compared to that of control membranes isolated from epithelial tissue, has been confirmed in two studies. One inherent problem in the approach is that the stimuli, primarily carbohydrate sweeteners, are not ideal model compounds to use, as they are not active at low concentrations and do not show sufficiently high binding-constants. The use of other stimulus compounds that are at least several hundred times sweeter than sucrose, such as saccharin, dihydrochalcone sweeteners, dipeptide sweeteners, stevioside, perillartine and other sweet oximes, the 2-substituted 5-nitroanilines, and... 

Molecular dynamics (MD) simulations are a class of molecular mechanics calculation which directly model the motions of molecular systems, often providing considerable information which cannot be obtained by any other technique, theoretical or experimental. MD simulations have only recently been applied to problems of carbohydrate conformation and motions, but it is likely that this technique will be widely used for modeling carbohydrates in the future. This paper introduces the basic techniques of MD simulations and illustrates the types of information which can be gained from such simulations by discussing the results of several simulations of sugars. The importance of solvation in carbohydrate systems will also be discussed, and procedures for including solvation in molecular dynamics simulations will be introduced and again illustrated from carbohydrate studies. 

Two aspects of carbohydrate structure are especially problematic for modeling because of the multiple minimum problem ... 

Models with three or more stereogenic centers create new problems. Again, carbohydrate chemists were first to give efficient and clear, though perhaps to the outsider cumbersome solutions. The following carbohydrate convention (see Table 11) is based on the Fischer projection. i.e., it prescribes an all-eclipsed conformation of the backbone and defines the direction of the backbone by the oxidation numbers of the terminal carbon atoms. 

The calculation of the electro-optical parameters describing Raman intensities is not yet very advanced, because of the paucity of data. Nevertheless, some success was achieved in calculations of the intensity of infrared absorption. The results on trans and gauche bond-rotation in ethylene glycol146 could be taken as a model for carbohydrates. Indeed, similar electro-optical parameters (/aCH, /aOH, /aCC, and /aCO) were calculated. This leads to the expectation that calculations of the intensity of the vibrational spectra of carbohydrates may be accomplished in the near future. In addition, the delicate problem of accounting for molecular interactions in calculating infrared intensities could be approached as it was for v(CCC) and i CO) vibrations in acetone.149 This will allow interpretation of weak, as well as strong, i.r. bands, in order to determine the structural properties of molecules. 

The reviews by Bishop and H. G. Jones gave tabular data on the retention times of methyl glycosides and other derivatives. Some papers concerned with the structure of carbohydrate materials provide much useful information on certain groups of compounds, and others examine model systems for the separation of a given class of sugar. This Section deals mainly with the latter type of study, and applications of these methods to structural problems will be discussed subsequently. 

The small size of hevein (43 residues), and the ease of its availability by biochemical purification or methods of peptide synthesis make this domain an excellent model system for the study of carbohydrate recognition by proteins. Herein, and taking the hevein domain as a model, we focus on the study of those molecular-recognition features relevant for the interactions between carbohydrates and proteins. We detail all of the techniques that are instrumental for tackling this problem, and how these can strategically be combined in an efficient manner. Particular emphasis is placed on the acquisition and analysis of data at atomic resolution (by NMR and/or X-ray ), and how these structural data relate with thermodynamic and kinetic information in reaching an understanding of the forces and interactions that play decisive roles in the interactions between carbohydrates and proteins. 

We are now preparing and studying membrane models formed by ternary systems amphipatic block copolymer/lipids/water. From the interaction with our polymeric models of lectins (lectins are proteins or glycoproteins specific of different sugar residues] we hope to obtain informations about the respective parts played by the different carbohydrate chains and the polypeptide skeleton of glycoproteins and perhaps help to throw some light on problems as important as cell recognition and cell contact inhibition. 

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