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Molecular dynamics simulations of alpha 2 -> 8-linked disialoside: Conformational analysis and implications for binding to proteins

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Title Molecular dynamics simulations of alpha 2 -> 8-linked disialoside: Conformational analysis and implications for binding to proteins
 
Creator VASUDEVAN, SV
BALAJI, PV
 
Subject t-cell activation
crystal-structure
d-glucose
3-dimensional structures
glycosidic linkage
polysialic acid
tetanus toxin
sialic-acid
oligosaccharides
polysaccharide
gangliosides
sialic acids
cell surface recognition
gromos
botulinum toxin
tetanus toxin
 
Description Computational methods have played a key, role in elucidating the various three-dimensional structures of oligosaccharides. Such structural information, together with other experimental data, leads to a better understanding of the role of oligosaccharide in various biological processes. The disialoside Neu5Ac-alpha2-->8-Neu5Ac appears as the terminal glycan in glycoproteins and glycolipids, and is known to play an important role in various events of cellular communication. Neurotoxins such as botulinum and tetanus require Neu5Ac-alpha2 --> 8-Neu5Ac for infecting the host. Glycoconjugates containing this disialoside and the enzymes catalyzing their biosynthesis are also regulated during cell growth. development, and differentiation. Unlike other biologically relevant disaccharides that have only two linkage bonds, the alpha2-8-linked disialoside has four: C2-O, O-C8', C8'-C7', and C7'-C6'. The present report describes the results from nine 1 ns MD simulations of alpha2-->8-linked disialoside (Neu5Ac-alpha2-->8-Neu5Ac); simulations were run using GROMOS96 by explicitly considering the solvent molecules. Conformations around the O-C8' bond are restricted to the +sc/+ap regions due to stereochemical reasons. In contrast. conformations around the C2-O and C8'-C7' bonds werefound to be largely unrestricted and all the three staggered regions are accessible. The conformations around the C7'-C6' bond were found to be in either the - sc or the anti region. These results are in excellent agreement with the available NMR and potential energy calculation studies. Overall, the disaccharide is flexible and adopts mainly two ensembles of conformations differing in the conformation around the C7'-C6' bond. The flexibility associated with this disaccharide allows for better optimization of intermolecular contacts while binding to proteins and this may partially compensate for the loss of conformational entropy that may be incurred due to disaccharide's flexibility. (C) 2002 John Wiley Sons, Inc.
 
Publisher JOHN WILEY & SONS INC
 
Date 2011-08-16T10:06:52Z
2011-12-26T12:54:53Z
2011-12-27T05:43:14Z
2011-08-16T10:06:52Z
2011-12-26T12:54:53Z
2011-12-27T05:43:14Z
2002
 
Type Article
 
Identifier BIOPOLYMERS, 63(3), 168-180
0006-3525
http://dx.doi.org/10.1002/bip.10019
http://dspace.library.iitb.ac.in/xmlui/handle/10054/9466
http://hdl.handle.net/10054/9466
 
Language en