title: Binding competition to the POPG lipid bilayer of Ca2+, Mg2+, Na+, and K+ in different ion mixtures and biological implication.
abstract: Ion mixtures are prevalent in both cytosol and the exterior of a plasma membrane with variable compositions and concentrations. Although abundant MD simulations have been performed to study the effects of single ion species on the structures of lipid bilayers, our understanding of the influence of the ion mixture on membranes is still limited; for example, the competition mechanism of different ions in binding with lipids is not clearly addressed yet. Here, microsecond MD simulations were carried out to study the effects of the mixtures of Ca(2+), Mg(2+), Na(+), and K(+) ions on a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) bilayer. It has been revealed that the binding efficiency of these ions with POPG lipids is in the following order, Ca(2+) > Mg(2+) > Na(+) > K(+). The binding free energy of Ca(2+) to the lipid bilayer is ~-4.0 kcal/mol, which is much lower than those of other ions. This result explains why the effects of the ion mixture on membranes are particularly sensitive to the concentration of calcium. The on-rates of different ions do not have a large difference, while the off-rate of Ca(2+) is 2-3 orders of magnitude smaller than those of the others. Therefore, the strongest binding affinity of Ca(2+) is mainly determined by its smallest off-rate. In addition, our study suggests that the structure of the lipid bilayer is influenced dominantly by the concentration of Ca(2+) ions. The simulation results also provide a good explanation for a variety of biological processes relevant to Ca(2+) and Mg(2+) regulations, such as membrane fusion.
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Mao
authors.forename: Yun
authors.initials: Y
authors.lastname: Du
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Cang
authors.forename: Jinan
authors.initials: J
authors.lastname: Wang
authors.forename: Zhuxi
authors.initials: Z
authors.lastname: Chen
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Yang
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D007477:Ions / Q000737:chemistry; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010715:Phosphatidylglycerols / Q000737:chemistry; D011188:Potassium / Q000737:chemistry / Q000378:metabolism*; D012964:Sodium / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D007477:Ions; D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D012964:Sodium; D008274:Magnesium; D011188:Potassium; D002118:Calcium