Glyco-Ligated Binders to Lectins: Multivalency vs Specificity

Here, we examine and compare different types of glycan-based binders to lectins, a class of carbohydrate-binding proteins involved in many biological recognition processes. We use atomistic molecular dynamics simulations to model metallosupramolecular glycoassemblies of different topologies, core charges, and linker lengths binding in a multivalent manner to glyco-recognizing domains in Concanavalin A (ConA), a well-studied plant lectin with specific affinity for mannose and glucose. We also designed and modeled a small peptidoglycan specifically bound to ConA. The obtained results reveal that despite their small size, simple peptidoglycans can have strong affinities to lectins, comparable to large multivalent supramolecular binders.