title: Specific Ion Binding at Phospholipid Membrane Surfaces.
abstract: Metal cations are ubiquitous components in biological environments and play an important role in regulating cellular functions and membrane properties. By applying metadynamics simulations, we have performed systematic free energy calculations of Na(+), K(+), Ca(2+), and Mg(2+) bound to phospholipid membrane surfaces for the first time. The free energy landscapes unveil specific binding behaviors of metal cations on phospholipid membranes. Na(+) and K(+) are more likely to stay in the aqueous solution and can bind easily to a few lipid oxygens by overcoming low free energy barriers. Ca(2+) is most stable when it is bound to four lipid oxygens of the membrane rather than being hydrated in the aqueous solution. Mg(2+) is tightly hydrated, and it shows hardly any loss of a hydration water or binding directly to the membrane. When bound to the membrane, the cations' most favorable total coordination numbers with water and lipid oxygens are the same as their corresponding hydration numbers in aqueous solution, indicating a competition between ion binding to water and lipids. The binding specificity of metal cations on membranes is highly correlated with the hydration free energy and the size of the hydration shell.
authors.affiliation: Department of Physics and Nuclear Engineering, Technical University of Catalonia-Barcelona Tech , B4-B5 Northern Campus, Jordi Girona 1-3, 08034 Barcelona, Catalonia, Spain.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for Polymer Studies and Department of Physics, Boston University , 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
authors.forename: Carles
authors.initials: C
authors.lastname: Calero
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bonomi
authors.affiliation: Department of Physics and Nuclear Engineering, Technical University of Catalonia-Barcelona Tech , B4-B5 Northern Campus, Jordi Girona 1-3, 08034 Barcelona, Catalonia, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Martí
mesh_terms: D001665:Binding Sites; D007477:Ions / Q000737:chemistry; D008672:Metals, Alkali / Q000737:chemistry*; D008673:Metals, Alkaline Earth / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000737:chemistry*; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D007477:Ions; D008672:Metals, Alkali; D008673:Metals, Alkaline Earth; D010743:Phospholipids