Molecular Modelling and Molecular Dynamics studies of GD1A, GD1B and their complexes with BoNT/B - Perspectives in interaction and specificity.

The conformational property for the oligosaccharide structure of GD1A and GD1B in aqueous environment is studied by 10ns Molecular Dynamics simulation using all atom model. Based on the trajectory analysis four conformational models are proposed for GD1A and one for GD1B. Direct and water mediated hydrogen bonding interactions plays a prominent role in stabilizing these conformational structures. The Molecular Modelling and 10ns MD simulation of Botulinum Neuro Toxin/B-GD1A and BoNT/B-GD1B complex revealed that this toxin can interact with GD1A in the single binding mode and with GD1B in two binding modes. Least mobility is seen for GD1A in the binding pocket of BoNT/B. The GTSM comparison, pair interaction energy calculation, total energy calculation, MM/PBSA binding free energy calculation and RMSD predicts that GD1A is a better receptor for BoNT/B compared to GD1B. The internal NeuNAc1 tends to form more than 70% of hydrogen bonds with BoNT/B both in GD1A and GD1B, hence specifying this particular site as a crucial space for the therapeutic design that can restrict the pathogenic activity of BoNT/B. Copyright © 2012 Elsevier Inc. All rights reserved.