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Full-atom models of membranes

Lipid bilayers and micelles of detergents

Elaboration of the database containing “equilibrium” structures of bilayers and micelles was carried out in our Laboratory. For this purpose we employed lipids and detergents differing in a charge of polar heads, length and saturation of acyl chains (fig.1). For all molecules corresponding force field topologies were created and/or optimized for Gromos87/96 (united atom force field). The common size of considered membrane systems is 100–200 lipid molecules / 5–7×10³ water molecules / 100–200 sodium ions (in a case of anionic lipids). All membranes were simulated in the liquid-crystaline state. During MD simulations the systems under study retain bilayer (or micellar) structure (fig 2.). Their macroscopic equilibrium averages (estimated on last 5–10 ns of MD) agree well with experimental data (table 1).

Structural and dynamic properties of model membranes strongly depend on the chemical nature of lipids. For instance, the charge of polar head provides different organization of the water–lipid interface of anionic and zwitterionic bilayers with the same acyl chains. Thus, it is looser in DOPC bilayer than that in DOPS one, thus making possible deeper penetration of water molecules inside the DOPC membrane (Polyansky et al., 2005; J. Phys. Chem).

Fig. 1. Structure of lipid molecules comprised model membranes.

Fig. 2. Snapshots of equilibrated DOPS bilayer (left panel) and SDS micelle (right panel). Lipids and waters are shown with sticks, sodium ions are given as blue spheres.

Cell membrane mimics

Application of mixed lipid bilayers close in composition of different cell membranes permits increasing feasibility of modeling of proteins and peptides in the membrane environment. According to experimental data about lipid composition and physico-chemical properties of membranes in gram negative bacteria (“Gram−”) and mammals erythrocytes (“Erythrocyte”) we elaborated following systems:

• “Erythrocyte” — POPC₁₁₄:POPE₁₁₄:CHOL₆₀ (80% POPC+POPE, 20% CHOL according to lipid composition of the human erythrocyte membrane);
• “Gram−” — POPE₂₀₀:POPG₈₈ (70% POPE, 30% POPG according to lipid composition of E. coli inner membrane).

Equilibrated structures of elaborated model membranes were obtained via MD simulations (~15 ns). Structural parameters of mixed membranes were adjusted based on packing characteristics of considered lipids in single-component bilayers.

Fig. 3. Model membranes “Erythrocyte” (left panel) and “Gram−” (right panel). Bilayers are shown with solvent accessible surface (top view). Lipids are colored as follows: POPC, POPE, POPG, CHOL.

These mixed bilayers are widely used in our current MD studies of antimicrobial peptides in explicit membranes (Polyansky et al., 2007, JBCB — in press).

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