Binding of Soluble Ligands to Membrane Receptors: A Molecular Dynamics Simulation Study.

The binding of membrane receptors to their ligands anchored in an apposing membrane mediates such biological processes as cell adhesion and signaling, and is known to be determined not only by direct receptor-ligand interactions but also by such factors as flexibility and thermal fluctuations of the apposing membranes. The binding of soluble ligands to membrane receptors initiates various cellular processes; however, to the best of our knowledge, its dependence on membrane properties has not been studied. Here, we employed molecular dynamics simulations to fill in this knowledge gap. Our simulations demonstrate that, in the absence of specific lipid-protein interactions and clustering of membrane receptors, the equilibrium and kinetic rate constants for the binding of soluble ligands to membrane receptors are determined almost entirely by direct receptor-ligand interactions and are practically unaffected by the curvature, flexibility and thermal fluctuations of the membrane.