What are Carbohydrates
Carbohydrates are poly hydroxy compounds which form a ring structure in water. The smallest building block is called a monosaccharide of which polysacharides consist of.
Example: D-glucose is shown in its linear (center), as a pyranose (>99% in water), and as a pentose. In this cyclyzation process an alpha (top right) and a beta anomer (bottom right) are formed which are shown in a ball and stick model (oxygen atom in red)
Example: Two disaccharides which consist of D-glucose units are shown. In maltose the glucose units are connected with anomeric center (1) in alpha configuration to the second unit at the 4 position. Cellobiose differs from maltose only in the configuration of the linking anomeric center. Consequently the corresponding polymers do have a different biological function. Starch which is the polymer of maltose can be digested by humans whereas cellulose cannot.
Why Study Carbohydrates
Carbohydrate-carbohydrate interactions are the initial step in cell recognition and in many other important biological processes.
Understanding these molecular interactions at atomic level will be valuable in the design of specific receptors for carbohydrates.
X-ray structures of glycoproteins do not often show a resolved carbohydrate part which make modeling studies even more important.
Modeling Project
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Development of the computational framework: Optimizing parameters of the potential energy functions.
- Pure liquid simulations: The parameters describing the inter-molecular interactions (q, A, C) are optimized to reproduce some physical properties such as the heat of vaporization and the density of a pure liquid.
- Rotational profiles: The parameters describing the intra-molecular interactions (V, q, A,C) are optimized to reproduce energetics of the conformations in the gas phase.
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Testing the Potential Energy Functions
Simple carbohydrates such as monosaccharides are in equilibrium between an alpha and a beta form in solution. This ratio is for many different monosaccharides experimentally determined. A first test of the computational framework is to reproduce this ratio using statistical perturbation theory.
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Example: One glucose molecule is solvated in a box of water molecules. The perturbation involves epimerisation at the carbinol center: Starting from the alpha anomer the beta hydroxy group is stepwise growing while the alpha hydroxy group is shrinking. A dummy atom is converted to a hydrogen atom and the hydrogen atom at the carbinolic center is converted to an oxygen atom. The sum of the energy differences calculated for each step are shown in the graph.
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Binding Studies: Host-Guest Complexes
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Example: Computer simulation of glucose bound to a cholaphane host (the solvent is omitted). During the simulation the free energy difference between the alpha and the beta anomer of glucose bound to the host is calculated (GC). Substracting this number from the free energy difference in solution (GG) leads to the free energy of binding which can be compared with the experiment (DDG).
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Wolfgang Damm, 29.09.97