Transforming binding affinities from three dimensions to two with application to cadherin clustering

Yinghao Wu, Jeremie Vendome, Lawrence Shapiro, Avinoam Ben-Shaul, Barry Honig

Research output: Contribution to journalArticlepeer-review

172 Scopus citations


Membrane-bound receptors often form large assemblies resulting from binding to soluble ligands, cell-surface molecules on other cells and extracellular matrix proteins. For example, the association of membrane proteins with proteins on different cells (trans-interactions) can drive the oligomerization of proteins on the same cell (cis-interactions). A central problem in understanding the molecular basis of such phenomena is that equilibrium constants are generally measured in three-dimensional solution and are thus difficult to relate to the two-dimensional environment of a membrane surface. Here we present a theoretical treatment that converts three-dimensional affinities to two dimensions, accounting directly for the structure and dynamics of the membrane-bound molecules. Using a multiscale simulation approach, we apply the theory to explain the formation of ordered, junction-like clusters by classical cadherin adhesion proteins. The approach features atomic-scale molecular dynamics simulations to determine interdomain flexibility, Monte Carlo simulations of multidomain motion and lattice simulations of junction formation. A finding of general relevance is that changes in interdomain motion on trans-binding have a crucial role in driving the lateral, cis-, clustering of adhesion receptors.

Original languageEnglish (US)
Pages (from-to)510-513
Number of pages4
Issue number7357
StatePublished - Jul 28 2011
Externally publishedYes

ASJC Scopus subject areas

  • General


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