Experimental verification of lipid bilayer structure through multi-scale modeling

Great progress has been made in applying coarse-grain molecular dynamics (CGMD) simulations to the investigation of membrane biophysics. In order to validate the accuracy of CGMD simulations of membranes, atomistic scale detail is necessary for direct comparison to structural experiments. Here, we present our strategy for verifying CGMD lipid bilayer simulations. Through reverse coarse graining and subsequent calculation of the bilayer electron density profile, we are able to compare the simulations to our experimental low angle X-ray scattering (LAXS) data. In order to determine the best match to the experimental data, atomistic simulations are run at a range of areas (in the NPNAT ensemble), starting from distinct configurations extracted from the CGMD simulation (run in the NPT ensemble). We demonstrate the effectiveness of this procedure with two small, single-component bilayers, and suggest that the greater utility of our algorithm will be for CGMD simulations of more complex structures.