TY - JOUR
T1 - Molecular modeling of the conformational and sodium ion binding properties of the oligosaccharide component of ganglioside GM1
AU - Rodgers, James C.
AU - Portoghese, Philip S.
PY - 1994/10
Y1 - 1994/10
N2 - The receptor‐like recognition behavior of the GM1 ganglioside has been examined theoretically in terms of conformational and binding properties. Modeling was conducted at two limiting conditions of dielectric constant in order to determine sensitivity to scaling of coulombic interactions. A systematic conformational search of the GM1 oligosaccharide in the absence of explicit solvent molecules indicates that there are many inherently low energy conformational states. Up to 39 conformers were found with energies within 5 kcal/mole of the observed lowest energy conformer. Using a dielectric constant of 80, a systematic search of sodium binding sites on GM1 identified 37 sites where a positively charged group might bind, while at least 12 sites were identified using a dielectric constant of 1. Notably important binding sites include pockets formed by the proximity of glycosidic (O1), sugar ring (O5), and exocyclic methylene hydroxyl (OH6) oxygens on the sugars. The oxygens of acetyl groups attached to sugars also contribute to the binding. Direct coordination with the carboxylate of sialic acid is not a prerequisite for cationic binding. The large number of conformational states and binding sites for the GM1 oligosaccharide are paradoxical to the specific recognition behavior of the molecule. This paradox can be explained in terms of bridging ligands, which are found from molecular dynamics to be capable of stabilizing molecular conformation. © 1994 John Wiley & Sons, Inc.
AB - The receptor‐like recognition behavior of the GM1 ganglioside has been examined theoretically in terms of conformational and binding properties. Modeling was conducted at two limiting conditions of dielectric constant in order to determine sensitivity to scaling of coulombic interactions. A systematic conformational search of the GM1 oligosaccharide in the absence of explicit solvent molecules indicates that there are many inherently low energy conformational states. Up to 39 conformers were found with energies within 5 kcal/mole of the observed lowest energy conformer. Using a dielectric constant of 80, a systematic search of sodium binding sites on GM1 identified 37 sites where a positively charged group might bind, while at least 12 sites were identified using a dielectric constant of 1. Notably important binding sites include pockets formed by the proximity of glycosidic (O1), sugar ring (O5), and exocyclic methylene hydroxyl (OH6) oxygens on the sugars. The oxygens of acetyl groups attached to sugars also contribute to the binding. Direct coordination with the carboxylate of sialic acid is not a prerequisite for cationic binding. The large number of conformational states and binding sites for the GM1 oligosaccharide are paradoxical to the specific recognition behavior of the molecule. This paradox can be explained in terms of bridging ligands, which are found from molecular dynamics to be capable of stabilizing molecular conformation. © 1994 John Wiley & Sons, Inc.
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U2 - 10.1002/bip.360341004
DO - 10.1002/bip.360341004
M3 - Article
C2 - 7948718
AN - SCOPUS:0028518840
SN - 0006-3525
VL - 34
SP - 1311
EP - 1326
JO - Biopolymers
JF - Biopolymers
IS - 10
ER -