Antibody Modeling Using Molecular Dynamics And Silcs Fragmaps

Antibodies are proteins produced by the immune system that are capable of binding to foreign invaders, typically other proteins or carbohydrates with high affinity and specificity which is central to their function. We use a combination of enhanced-sampling molecular-dynamics (MD) simulation and site-identification by ligand competitive saturation (SILCS) FragMaps to explore and identify conformations of the Fc, its mode of binding to glycan, and its interaction with EndoS and EndoS2, two endo-β-N-acetylglucosaminidase. Both EndoS and EndoS2 are secreted by the human pathogen Streptococcus pyogenes to deglycosylate the conserved N-linked glycan at N297 of IgG Fc to evade the immune system. Studies include the glycan in isolation and the Fc with both one and two glycans, thereby providing information on the impact of glycan to the FC stability, impact of FC on glycan conformational preference, and insight on the protection of glycosylation on aggregation of the Fc. The results provide conformations of glycan that could be accessible for both FC binding and to the Endoglycosidases.