@article { ISI:000293167900043,
	title = {Transforming binding affinities from three dimensions to two with application to cadherin clustering},
	journal = {NATURE},
	volume = {475},
	year = {2011},
	month = {JUL 28},
	pages = {510-U107},
	abstract = {Membrane-bound receptors often form large assemblies resulting from binding to soluble ligands, cell-surface molecules on other cells and extracellular matrix proteins(1). For example, the association of membrane proteins with proteins on different cells (trans-interactions) can drive the oligomerization of proteins on the same cell(2) (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(3). 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.},
	issn = {0028-0836},
	doi = {10.1038/nature10183},
	author = {Wu, Yinghao and Vendome, Jeremie and Shapiro, Lawrence and Ben-Shaul, Avinoam and Honig, Barry}
}
