An implicit solvent coarse-grained lipid model with correct stress profile

Abstract

We develop a coarse-grained parametrization strategy for lipid membranes that we illustrate for a dipalmitoylphosphatidylcholine bilayer. Our coarse-graining approach eliminates the high cost of explicit solvent but maintains more lipid interaction sites. We use a broad attractive tail-tail potential and extract realistic bonded potentials of mean force from all-atom simulations, resulting in a model with a sharp gel to fluid transition, a correct bending modulus, and overall very reasonable dynamics when compared with experiment. We also determine a quantitative stress profile and correct breakdown of contributions from lipid components when compared with detailed all-atom simulation benchmarks, which has been difficult to achieve for implicit membrane models. Such a coarse-grained lipid model will be necessary for efficiently simulating complex constructs of the membrane, such as protein assembly and lipid raft formation, within these nonaqueous chemical environments.

Systematic implicit solvent coarse graining of dimyristoylphosphatidylcholine lipids

“…The idea of uniting atoms into coarse‐grain (CG) sites (coarse graining) to reduce the number of degrees of freedom turned out to be very fruitful in application to lipid bilayers. A number of various models were reported during the past two decades . In general, they can be divided into two groups, so called top‐down and bottom‐up methodologies.…”

“…The first one requires the CG‐model to reproduce experimentally measurable macroscopic properties of the system without considering much of microscopic details . Typically, in this group of models lipids are represented as rigid rods or bead‐spring molecules, with a soft core repulsion or Lennard–Jones potential for the nonbonded interactions.…”

“…Later models represent a lipid molecule with more details: three beads connected in a rigid or flexible rod, or a polymer‐like five‐bead chain with constrained or elastic bonds . More advanced models take into account chemical structure of phospholipids, that is, two hydrocarbon tails introduced explicitly . The probably most known and widely used empirically parameterized model is formulated in terms of Martini force field, with coarse‐grained beads representing groups of about four heavy atoms and interactions parameterized using experimentally known thermodynamic data …”

Importance of Force Decomposition for Local Stress Calculations in Biomembrane Molecular Simulations

“…16,17 The lateral pressure is also frequently used to assess whether coarse-grained models reproduce the mechanical properties of atomistic systems. [18][19][20] Obtaining experimental measurements of the local stress within a membrane is very challenging, with few studies that have used fluorescent probes to measure changes in the internal stress. 21,22 Molecular dynamics (MD) simulations are increasingly being used to evaluate the stress tensor in lipid bilayers from atomistic [23][24][25][26][27][28][29][30] and coarse-grained 19,20,27,[30][31][32] models.…”

Hybrid Approach for Highly Coarse-Grained Lipid Bilayer Models

“…This profile is qualitatively consistent with other lipid models. 92,96,40,45,48,44 The lateral pressure profile can be broadly divided into three distinct zones for analysis. The first zone marks the extreme left and right of the profile and represents the head group and solvent interface region of the all-atom lipid system.…”