Molecular dynamics simulations and neutron reflectivity as an effective approach to characterize biological membranes and related macromolecular assemblies.

In combination with other spectroscopy, microscopy, and scattering techniques, neutron reflectivity is a powerful tool to characterize biological systems. Specular reflection of neutrons provides structural information at the nanometer and subnanometer length scales, probing the composition and organization of layered materials. Currently, analysis of neutron reflectivity data involves several simplifying assumptions about the structure of the sample under study, affecting the extraction and interpretation of information from the experimental data. Computer simulations can be used as a source of structural and dynamic data with atomic resolution. We present a novel tool to compare the structural properties determined by neutron reflectivity experiments with those obtained from molecular simulations. This tool allows benchmarking the ability of molecular dynamics simulations to reproduce experimental data, but it also promotes unbiased interpretation of experimentally determined quantities. Two application examples are presented to illustrate the capabilities of the new tool. The first example is the generation of reflectivity profiles for a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer from molecular dynamics simulations using data from both atomistic and coarse-grained models, and comparison with experimentally measured data. The second example is the calculation of lipid volume changes with temperature and composition from all atoms simulations of single and mixed 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC) bilayers.