Salt induced asymmetry in membrane simulations by partial restriction of ionic motion

Abstract

The specific ionic composition differs considerably at both sides of biological membranes and specific lipid/electrolyte interactions may be essential for their structure, stability and function. Hence, explicit consideration of the ionic asymmetry is important to achieve an accurate description of lipid bilayers. Molecular dynamics simulations have proven to be a reliable tool to study biomembranes at atomic detail. Nevertheless, the use of periodic boundary conditions allows ions to diffuse rapidly and reach both sides of the bilayer. Therefore, ad hoc simulation schemes have to be applied to take into account ionic asymmetry. In this work we present a simple implementation to overcome this problem. A more realistic description of the biomembranes can be achieved by partially restricting the ionic motion in the direction normal to the membrane within a region of the space near to only one of the leaflets. This creates two different situations: one leaflet is highly exposed to ions while the second one can be completely or partially depleted of them. Comparison between this new method and control simulations performed using a previously proposed approach consisting of a double-membrane setup yielded an excellent agreement with a speed-up of nearly 60%. The performance of the method with different ionic species is explored and remaining limitations are examined.

Structure and dynamics of nano-sized raft-like domains on the plasma membrane

“…The cutoff used for the restriction of the ionic motion was chosen to be 1.8 nm as it was used and discussed in our previous work. 28 The amount of water molecules in all the cases produced a separation between the average planes of both leaflets (between two consecutive images within the PBC) of nearly 5 nm. This leaves a layer of bulk water with a thickness ≥1 nm.…”

“…28 This method restricts the motion of the ions in the direction perpendicular to the membrane plane. In this way we have the extracellular leaflet highly exposed to Na + and Ca 2+ and the intracellular side highly exposed to K + .…”

“…This gauge was chosen since it is comparable to experimental measurements of the thickness using the Luzzati method 53, 54 where the position of the phosphorus group can be interpreted as the location of the Luzzati interface and it is commonly used in membrane simulations. 28,45,55 Contour levels were calculated by mapping the position of the phosphorous atoms onto a 0.5 nm grid (with the positions averaged for all the frames on each monolayer). The order parameters were calculated for the C5 carbons as these positions roughly correspond to the center of the lipid tails and it is in contact with the cholesterol molecules.…”

“…An important feature in our simulations is the incorporation of ionic asymmetry at both sides of the membrane. As the interaction with cations, especially sodium, introduces an increment of nearly 10% in the thickness, 28 Density profiles. A comprehensive view of the distribution of the different components of the system can be acquired from the number density profile along the z axis calculated for all the systems during the last 50 ns of simulation (Figures 2(a) and 2(b)).…”

Modeling complex biological systems: From solution chemistry to membranes and channels

“…This approach has subsequently been used by several groups to study the permeation of ion channels [19,20]. Herrera and Pantano proposed a variation of the method where ionic motion is restricted anisotropically to one side of the system [21]. Finally, Bostick et al used vacuum slabs to separate the compartments of a single unit cell [22].…”