Bending Lipid Bilayers: A Closed-Form Collective Variable for Effective Free-Energy Landscapes in Quantitative Biology

J Chem Theory Comput. 2018 Apr 10;14(4):2240-2245. doi: 10.1021/acs.jctc.8b00012. Epub 2018 Mar 9.

Abstract

Curvature-related processes are of major importance during protein-membrane interactions. The illusive simplicity of membrane reshaping masks a complex molecular process crucial for a wide range of biological functions like fusion, endo- and exocytosis, cell division, cytokinesis, and autophagy. To date, no functional expression of a reaction coordinate capable of biasing molecular dynamics simulations to produce membrane curvature has been reported. This represents a major drawback given that the adequate identification of proper collective variables to enhance sampling is fundamental for restrained dynamics techniques. In this work, we present a closed-form equation of a collective variable that induces bending in lipid bilayers in a controlled manner, allowing for straightforward calculation of free energy landscapes of important curvature-related events, using standard methods such as umbrella sampling and metadynamics. As a direct application of the collective variable, we calculate the bending free energies of a ternary lipid bilayer in the presence and the absence of a Bin/Amphiphysin/Rvs domain with an N-terminal amphipathic helix (N-BAR), a well-known peripheral membrane protein that induces curvature.

MeSH terms

  • Autophagy
  • Cell Division
  • Entropy*
  • Lipid Bilayers / chemistry*
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • Proteins / chemistry

Substances

  • Lipid Bilayers
  • Proteins