Biopolymer



4       Carbohydrate Model Building

 Carbo is a pulldown in the Biopolymer module which contains commands which allow you to construct polysaccharides, alter or change an existing monosaccharide in a polysaccharide and join polysaccharides together.

This chapter describes how to build models of oligo- and polysaccharides from monosaccharides. Read this chapter if you are planning on doing carbohydrate model building.

To fully understand the concepts covered here, it is recommended that you work through the available Pilot tutorials. Descriptions of individual commands can be found using the Help/Insight_Help command in Insight II.


Introduction

Carbohydrates are an important class of biological macromolecules, found in nature both in isolation as mono-, oligo- and polysaccharides and in association with other biological macromolecules, e.g., as glycolipids and glycoproteins. They are involved in a diverse range physiological roles such as molecular recognition, energy storage, enzyme regulation, etc.

Biopolymer contains a number of predefined monosaccharides that can be used as building blocks for constructing both linear and branched oligo- or polysaccharides. These features are accessed via the Carbo pulldown in the Biopolymer module.


Tutorials

Biopolymer Lesson 4 consists of two Pilot tutorial scripts that demonstrate the construction of carbohydrate biomolecules.

To start Pilot, click the mortarboard icon on the Insight II toolbar. When the Pilot interface appears, click Select and choose the Biopolymer tutorials from the list.

Select one of the following:

and click the Select button. Run the tutorial by clicking either of the two leftmost buttons at the top of the Pilot window.

These two buttons will execute a single command from the tutorial. The leftmost button executes commands without displaying the graphical user interface, while the adjacent button displays the interface containing predefined command parameters and waits for the user to click the execute button in the user interface parameter block.


Methodology and implementation

Monosaccharide building blocks

 The Carbo pulldown in the Biopolymer module contains a series of commands designed to facilitate carbohydrate model construction. In addition, the user interface is designed with the carbohydrate chemist in mind and uses torsion angle, linkage types, etc., that will be familiar to many carbohydrate chemists.

The primary building block of carbohydrate model building is the monosaccharide. The carbohydrate fragment library used in the Fragment/Get command provides only two basic monosaccharides. These are the -D variants of the five membered ring compound ribose and the six membered ring compound glucose. The Carbo/Get command provides a larger set of monosaccharides:

These are available in / variants, which differ in configuration at the anomeric carbon C1, and/or in D/L variants are mirror images. Ring atom numbering is illustrated in Figure 6.

Oligosaccharide model building

To construct a polysaccharide you need to retrieve many monosaccharides and combine them using either the Carbo/Append or Carbo/Join command. The process of joining together two polysaccharides entails a dehydration reaction. However, as in other bonding operations in Insight II, negligible side products such as water are automatically deleted. So the result of the Carbo/Append and Carbo/Join commands is always one molecule, the carbohydrate -- not two molecules, the carbohydrate and the water.

When you combine one polysaccharide with another you must specify which bond sites on which monosaccharides are to be used in linking the two. Bonding site carbons in a monosaccharide are numbered 1, 2, 3... These carbons are named C1, C2, C3... and are determined by their position in the ring (see Figure 6). For example, the C3 linkage site is the hydroxyl off the third carbon away from the ring oxygen in the direction of the anomeric carbon. Bond sites greater than the number of ring carbons are found by continuing the count into the carbons of the bulky group. The commands in the Carbo pulldown in Insight II are based on ring monosaccharides. The straight chain monosaccharides are not recognized.

Figure 6 . Examples of 5- and 6-membered rings

You also need to specify the dihedral angles used to determine the secondary structure. The torsion angles and are definable. However, Insight II provides the default values of 60° for a linkage and -60° for an linkage. The angle defaults to 0°. The and angles for the 1 3 linkage shown in Figure 7 are determined by the atoms: = H1-C1-O3´-C3´ and = C1-O3´-C3´-H3´.

Figure 7 . A (1 3) Linkage showing at torsion angle H1-C1-O3´-C3´ and at torsion angle C1-O3´-C3´-H3´

Note that the valid linkage type provided in the Linkage List value aid only cover the 1-1, 1-2, 1-3, 1-4, 1-6 and 2-8 types. Other linkage types, e.g., 2-3, can be used in the Carbo/Append and Carbo/Join commands, but these must be typed in when the Linkage user interface parameter is selected.

Modifying an existing carbohydrate

Having built a carbohydrate using the Carbo/Get, Carbo/Append and Carbo/Join commands, or after loading an existing carbohydrate model, further editing may be performed using the following carbohydrate editing commands.

In order to alter the anomeric (C1) configuration of a single monosaccharide in a carbohydrate model the Carbo/Alpha_Beta command can be used. The anomeric form is selected as either or using the Anomer parameter and the monosaccharide to be altered may be picked with the mouse. Similarly, a single monosaccharide may be altered between the D/L forms using the Carbo/L_D command. This command merely changes the sign of the Z coordinate for each atom in the selected monosaccharide or monomer.

Replacement of one monosaccharide in an existing carbohydrate model with another monosaccharide can be performed using the Carbo/Replace command. The Monomer to Replace parameter allows the user to pick the monosaccharide to be replaced while the Monosaccharide parameter allows a selection of potential replacements from a list. The replacement monosaccharide can be of / anomeric form and of D/L configuration. This command will retain linkage sites and - torsion angles across the affected glycosidic linkages. Other conformational data, such as exocyclic OH torsion angles for the original monosaccharide, are not preserved. Invalid operations, such as attempting to use a 5-membered ring to replace a 6-membered ring in which a 4-n linkage exists, are not allowed.



Last updated September 30, 1997 at 11:31AM PDT.
Copyright © 1997, Molecular Simulations, Inc. All rights reserved.