Computer simulations of a heterogeneous membrane with enhanced sampling techniques.

Yevhen K. Cherniavskyi,D. Peter Tieleman,Ron Elber,Arman Fathizadeh

doi:10.1063/5.0014176

Abstract

Computational determination of the equilibrium state of heterogeneous phospholipid membranes is a significant challenge. We wish to explore the rich phase diagram of these multi-component systems. However, the diffusion and mixing times in membranes are long compared to typical time scales of computer simulations. Here, we evaluate the combination of the enhanced sampling techniques molecular dynamics with alchemical steps and Monte Carlo with molecular dynamics with a coarse-grained model of membranes (Martini) to reduce the number of steps and force evaluations that are needed to reach equilibrium. We illustrate a significant gain compared to straightforward molecular dynamics of the Martini model by factors between 3 and 10. The combination is a useful tool to enhance the study of phase separation and the formation of domains in biological membranes.

Highlights

Biological membranes are complex environments that function as a semi-permeable barrier between the cell interior and the external environment
The atomically detailed calculations were attempted with Molecular Dynamics with Alchemical Steps (MDAS)
With Monte Carlo (MC)-Molecular Dynamics (MD), we see a similar trend toward a significant increase in the weight of Coulomb interactions in the total work during an exchange move: 16% (1.07 kcal/mol) of work comes from Coulomb interactions and 84% (5.48 kcal/mol) from VdW with the non-polarizable water model

Summary

Introduction

Biological membranes are complex environments that function as a semi-permeable barrier between the cell interior and the external environment. They consist of phospholipids, cholesterol and protein molecules, and more. A number of experimental techniques such as x-ray and neutron scattering, nuclear magnetic resonance (NMR), and others provide structural data on lipid membranes. Scattering-based techniques can directly probe the spatial organization of lipid membranes without introducing additional probes that alter the membrane structure.. The scattering signal is a spatial and temporal average over many fluid structures, leading to a smooth and less detailed signal. The averaging and separation of signals is even more difficult in mixed membranes with multiple types of phospholipids.

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Discussion

Conclusion