An illustration of Computational Carbohydrate Grafting (CCG) method applied to predict binding conformations of TF-containing glycans binding to the JAA-F11 antibody.

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posted on 2013-01-24, 00:34 authored by Matthew B. Tessier, Oliver C. Grant, Jamie Heimburg-Molinaro, David Smith, Snehal Jadey, Andrew M. Gulick, John Glushka, Susan L. Deutscher, Kate Rittenhouse-Olson, Robert J. Woods

Upper. Examples of glycans that bind to JAA-F11: Neu5Acβ2-6(Galβ1-3)GalNAcα (2); Neu5Acα2-6(Galβ1-3)GalNAcα (3); Galβ1-4GlcNAcβ1-6(Galβ1-3)GalNAcα (4), as well as non-binding sequences (middle): Fucα1-2Galβ1-3GalNAcα (10); GlcNAcβ1-3Galβ1-3GalNAcα (11); and Neu5Acα2-6(Neu5Acα2-3Galβ1-3)GalNAcα (23), showing the minimal binding determinant in red, the tolerated glycan branches in green, and the disallowed branches in grey. Also presented are the combined solvent-accessible surfaces from a superimposition of the sequences based on aligning the minimal determinant. Lower. In the grafting process branches from TF-containing glycans in the library are excised and spliced onto the bound minimal determinant. The grafted branches are then assessed for steric clashes with the antibody surface. This process is illustrated for the grafting of the glycan branch Galβ1-4GlcNAcβ1-6 (green carbon frame) from 4 onto the TF antigen in the JAA-F11 binding site (yellow solvent-accessible surface). Figures generated with Chimera [52].