Chemistry Reference
In-Depth Information
Structural Database; www.ccdc.cam.ac.uk). Data on complex glycoconjugates,
various polysaccharides and carbohydrates in complex with proteins (X-ray and
NMR structures) are also available in the public domain (see Brookhaven Protein
Database; www.rcsb.org; for example on illustrations of protein-sugar complexes,
please see Figure 16.1). Information on carbohydrate-protein complexes is acces-
sible in the receptor-ligand database (Relibase; http://www.ccdc.cam.ac.uk/free_
services/relibase_free). Other experimental methods important for structural
studies such as mass spectrometry (see Chapter 5 on structural aspects) or circular
dichroism do not provide direct information on atomic coordinates and essentially
require correlations with NMR data or molecular modeling. Therefore, to gain a
full understanding of the three-dimensional attributes of carbohydrates in solution
(i.e., the shape and the dynamics of its alterations) a strategic combination of
experimental methods with molecular modeling is required;
in silico
protocols
having thus become an indispensable tool [1] .
Computer modeling of carbohydrates started around 40 years ago on a simple
platform based on a trouble- free ' allow ' and ' reject ' approach for conformations
judged to be possible owing to interatomic distances. Further progress in this fi eld
resulted in the development of powerful computational tools, built on contempo-
rary ' state
-
of-the-art' hardware (cluster and grid computing) and software (quantum
and molecular mechanics, molecular dynamics, Monte Carlo, and so on) applica-
ble to glycosciences. Various custom- made carbohydrate - modeling tools are pub-
licly available at www.glycosciences.de. They facilitate
in silico
building of
oligosaccharide structures and calculations of their conformational features. In
addition, conformational energy maps for selected oligosaccharides are also acces-
sible at this resource. To guide the reader to an understanding of the conforma-
tional behavior of oligosaccharides we start our tour through the realm of
computational glycochemistry by identifying the levels of complexity.
2.2
Complexity of Carbohydrate Flexibility
The following parameters are tied to the spatial appearance of glycans: the confor-
mation of the monosaccharide rings (either fi ve-membered furanose or six-
membered pyranose rings; please see Chapter 1), the mutual orientation of the
rings specifi ed in terms of fl exibility around a glycosidic bond, and the positions
of the side chains attached to these rings. All of these factors infl uence the molecu-
lar shape, partial charge distribution, formation of intra- and inter- residual hydro-
gen bonds, solvent accessibility, and bonding ability to proteins and other
biomacromolecules [2]. Due to the apparent complexity of this issue, we start by
defi ning in further detail the fl exibility at the level of the building blocks (i.e., the
monosaccharides).
