Poster abstracts
Poster number 48 submitted by Brandon Neel
Large scale molecular dynamics simulations of cadherins involved in cell adhesion
Brandon Neel (Ohio State University, OSBP), Raul Araya-Secchi (University of Copenhagen, Niels Bohr Institute), Marcos Sotomayor (Ohio State University, Department of Chemistry & Biochemistry)
Abstract:
Cadherins are a family of proteins responsible for intercellular adhesion between epithelial cells and for maintaining tissue integrity. Epithelial cadherin, found in adherens junctions, is a ubiquitous classical-type cadherin that has five extracellular cadherin (EC) repeats. Epithelial cadherin links adjacent cells through a tip-to-tip interaction mediated by an exchange of conserved tryptophan residues in their distal EC repeats. Here we present large-scale molecular dynamics simulations that model the complete extracellular domains of available E-cadherin crystal structures, with systems encompassing up to 5 million atoms. Equilibrium and steered molecular dynamics simulations of E-cadherin lattices predict a two-phase elastic response in which E-cadherin complexes first straighten and then unbind without unfolding. Cis-interactions are predicted to play a minor role in the mechanical response of these complexes. Overall, our simulations provide insights into the molecular mechanics of adherens junctions.
Keywords: Molecular Dynamics Simulations, Cadherins, Cell Adhesion