MOLECULAR-DYNAMICS SIMULATIONS OF A MONOFUCOSYLATED BIANTENNARY GLYCAN OF THE N-ACETYLLACTOSAMINE TYPE - THE HUMAN LACTOTRANSFERRIN GLYCAN

Molecular dynamics simulations were carried out to explore the conformational flexibility of the antennae of N-linked glycans. They were performed over 200 ps in vacuo on the complete disialylated monofucosylated biantennary glycan of the N-acetyllactosaminic type. Starting from a bird-conformation, the 3-D-structure evolved through 9 successive transitional states to a new, compact and energetically favorable conformation which had never been previously described. In this conformation, both antennae are organized in two coplanar loops rolled in a contrary direction and oriented perpendicularly to the plane of the di-N-acetyl chitobiose residue leading to a 'lobster conformation'. All the glycosidic linkages of the disialylated monofucosylated biantennary glycan, except the Fuc(alpha-1-6)GlcNAc(beta-1-), were modified by a phase transition. Particularly, the Man(beta-1-4) GlcNAc(beta-1-) linkage, which was previously described by NMR and X-ray diffraction as a rigid one, was involved in numerous conformational changes during 83 ps, even before the first transition phase. The freedom of mobility of the torsional angles of the Man(alpha-1-6)Man(beta-1-) linkage was limited, under these simulation conditions, to the angle psi which took three values: 30-degrees, 90-degrees and 180-degrees. Moreover, from 150 ps up to the end of the simulation, the value of the torsional angle omega of the NeuAc(alpha-2-6)Gal(beta-1-) linkage of the alpha-1,6-antenna continuously swung between 60-degrees and -60-degrees. Finally, we observed that the values of the torsional angles of the three linkages: NeuAc(alpha-2-6)Gal(beta-1-), Gal(beta-1-4)GlcNAc(beta-1-) and GlcNAc(beta-1-2)Man(beta-1-) of each of the two antennae were different, demonstrating their asymmetric conformation.