Elucidation of the LewisX–LewisX carbohydrate interaction with molecular dynamics simulations: A glycosynapse model

Abstract

Carbohydrates play vital roles in many biological processes, such as recognition, adhesion and signaling between cells. The LewisX determinant is a trisaccharide fragment implicated as a specific differentiation antigen, tumor antigen and key component of the ligand for the endothelial leukocyte adhesion molecule. The interaction between LewisX and LewisX was found to be homotypic and calcium mediated. Diverse techniques have been used to investigate this interaction, but poor informations are available about the geometry and the dimerization mechanism. In this work, we report the first molecular model of this homotypic interaction. Two molecular dynamics simulations were done in explicit solvent with and without calcium ions. Trajectory analysis and comparisons yielded deep informations about the energetics and insights into the role and stoichiometry of interacting calcium ions. Furthermore, two specifics complexes structures are observed and proposed as key pathways in cellular signal transduction, called glycosynapse, of the LewisX epitope.