Predicting and interpreting EPR spectra of POPC lipid bilayers with transmembrane α-helical peptides from all-atom molecular dynamics simulations†

Abstract

This study reports a large-scale all-atom MD simulation of POPC lipid bilayers in the presence of different concentrations of the transmembrane peptide acetyl-K₂(LA)₁₂K₂-amide ((LA)₁₂) and doped with 5-PC paramagnetic spin probes used in EPR studies. We apply a combined MD-EPR simulation methodology for the prediction of EPR spectra directly and completely from MD trajectories. This approach serves three major purposes. Firstly, comparing predicted EPR spectra with experimental ones, which are highly sensitive to motions, provides an ultimate test bed for the force fields currently employed for modeling lipid bilayer systems with embedded proteins or peptides. Secondly, simulations of EPR spectra directly from the atomistic MD models simplify the interpretation of the EPR line shapes and their changes induced by the presence of peptides in the lipid bilayer. These changes are directly linked to the dynamics and order of spin probes and POPC host molecules. Lastly and importantly, we demonstrate how the MD-EPR methodology can be employed to test the validity and limitations of the widely used approach for the estimation of the order parameter of lipids directly from the EPR experimental line shapes.