Implicit solvent systematic coarse-graining of dioleoylphosphatidylethanolamine lipids: From the inverted hexagonal to the bilayer structure.

Saeed Mortezazadeh,Yousef Jamali,Alexander P Lyubartsev,Hossein Naderi-Manesh

doi:10.1371/journal.pone.0214673

Saeed Mortezazadeh, Yousef Jamali + Show 2 more

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https://doi.org/10.1371/journal.pone.0214673

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Abstract

Lamellar and hexagonal lipid structures are of particular importance in the biological processes such as membrane fusion and budding. Atomistic simulations of formation of these phases and transitions between them are computationally prohibitive, hence development of coarse-grained models is an important part of the methodological development in this area. Here we apply systematic bottom-up coarse-graining to model different phase structures formed by 1,2-dioleoylphosphatidylethanolamine (DOPE) lipid molecules. We started from atomistic simulations of DOPE lipids in water carried out at two different water/lipid molar ratio corresponding to the lamellar Lα and inverted hexagonal HII structures at low and high lipid concentrations respectively. The atomistic trajectories were mapped to coarse-grained trajectories, in which each lipid was represented by 14 coarse-grained sites. Then the inverse Monte Carlo method was used to compute the effective coarse-grained potentials which for the coarse-grain model reproduce the same structural properties as the atomistic simulations. The potentials derived from the low concentration atomistic simulation were only able to form a bilayer structure, while both Lα and HII lipid phases were formed in simulations with potentials obtained at high concentration. The typical atomistic configurations of lipids at high concentration combine fragments of both lamellar and non-lamellar structures, that is reflected in the extracted coarse-grained potentials which become transferable and can form a wide range of structures including the inverted hexagonal, bilayer, tubule, vesicle and micellar structures.

Highlights

Phospholipids are the main ingredients of the cell membranes that separate cells from their surrounding
Since the bottom-up approaches are known to be dependent on the thermodynamic state of the system, atomistic simulations of DOPE molecules were performed under two different water contents corresponding to conditions of the lamellar and inverted hexagonal phases
We investigated two sets of CG potentials derived from atomistic simulations carried out at different thermodynamics conditions corresponding

Summary

Introduction

Phospholipids are the main ingredients of the cell membranes that separate cells from their surrounding. The Martini model [12] is the most famous model of this type which exploits the standard form of molecular mechanical force field with Lennard-Jones and electrostatic potential energy functions for non-bonded interactions and harmonic potential functions for bond and angle interactions Both approaches have their own advantages and limitations which can be very generally summarized that the bottom-up approach is better suitable to capture specific details of the interactions between the involved molecules whereas the top-down approach provides a force field framework that usually can be extended to other systems [13]. In this work we investigated phase behaviour of 1,2-dioleoylphosphatidylethanolamine (DOPE) lipids, which form inverted hexagonal (HII) phase at low water content and bilayer (Lα) structures [26, 27] at high water content For this purpose we developed a solvent-free CG model of DOPE lipid using systematic structure-based coarse-graining. Since the bottom-up approaches are known to be dependent on the thermodynamic state of the system, atomistic simulations of DOPE molecules were performed under two different water contents corresponding to conditions of the lamellar and inverted hexagonal phases

Methods

Results and discussions

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Conclusions