Antibody-Carbohydrate Recognition from Docked Ensembles Using the AutoMap Procedure

Abstract

Carbohydrate-protein recognition is vital to many processes in health and disease. In particular, elucidation of the structural basis of carbohydrate binding is important to the development of oligosaccharides and oligosaccharide mimetics as vaccines for infectious diseases and cancer. Computational structural techniques are valuable for the study of carbohydrate-protein recognition due to the challenges associated with experimental determination of carbohydrate-protein complexes. AutoMap is a computer program that we have developed to study protein-ligand recognition. AutoMap determines the interactions taking place in a set of highly ranked poses obtained from molecular docking and processes these to identify the protein residues most likely to be involved in interactions. In this protocol, we describe the use of AutoMap and illustrate its suitability for studying antibody recognition of the Lewis Y tetrasaccharide, which is a potential cancer vaccine antigen.

Molecular Simulations of Carbohydrates with a Fucose-Binding Burkholderia ambifaria Lectin Suggest Modulation by Surface Residues Outside the Fucose-Binding Pocket

“…We have demonstrated that, as the result of all the above-mentioned challenges, docking programs and scoring functions are not always able to predict the native binding pose faithfully as the top docked pose. To overcome this shortcoming and to harness the recognition information embedded in the docking output, we have developed a site mapping methodology that takes into account an ensemble of docked poses and identifies binding site residues critically involved in recognition of a ligand or ligand family (Yuriev et al, 2001 , 2002 ; Agostino et al, 2013 ; Dingjan et al, 2015a ).…”

“…All BambL-blood group carbohydrate complexes were examined using LigPlot (Wallace et al, 1995 ; Laskowski and Swindells, 2011 ). Only poses that passed the glycosidic torsion filter requirements (see above), were used for site mapping, following a previously developed method (Yuriev et al, 2001 ; Agostino et al, 2009b , 2011 , 2013 ; Dingjan et al, 2015a ). In brief, each individual hydrogen bond made by a particular BambL residue was counted toward the hydrogen-bond tally.…”