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

BUSTOS, DIEGO M.; BUSTOS, DIEGO M.; UHART, MARINA; UHART, MARINA; MASONE, DIEGO; MASONE, DIEGO

JOURNAL OF CHEMICAL THEORY AND COMPUTATION

AMER CHEMICAL SOC

Lugar: Washington, D.C.; Año: 2018 vol. 14 p. 2240 - 2245

1549-9618

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.