Lipid Bilayer Structure Refinement with Saxs/Sans Based Restrained Ensemble Molecular Dynamics

Abstract

Small angle scattering is a powerful technique that can probe the structure of lipid bilayers on the nanometre scale. Retrieving the real space structure of lipid bilayers from the scattering intensity can be a challenging task, as the fluid nature of lipid bilayers results in a liquid-like scattering pattern which is hard to interpret. The standard approach to this problem is to describe the bilayer structure as a sum of density distributions of separate components of the lipid molecule and then fit the parameters of the distributions against experimental data. The accuracy of the density-based analysis is partially limited by the choice of the functions which are used to describe component distributions, especially in the case of multicomponent bilayers. The number of parameters in the model is balanced by the need for an accurate description of the underlying bilayer structure and the risk of overfitting the data. Here we present an alternative method for the small angle scattering intensity interpretation for lipid bilayers. The method is based on restrained ensemble molecular dynamics simulations, that allow direct incorporation of the scattering data into the simulations in the form of a restraining potential. This approach combines the information that is implicitly contained in the force field used for the simulation with structural data from the scattering intensity and is free from prior assumptions regarding the bilayer structure.