Fat SIRAH: Coarse-grained phospholipids to explore membrane-protein dynamics

Abstract

ABSTRACTTne capability to handle highly heterogeneous molecular assemblies in a consistent manner is among the greatest challenges faced when deriving simulation parameters. This is particularly the case for coarse-grained simulations in which chemical functional groups are lumped into effective interaction centers for which transferability between different chemical environments is not guaranteed. Here we introduce the parameterization of a set of CG phospholipids compatible with the latest version of the SIRAH force field for proteins. The newly introduced lipid species include different acylic chain lengths, partial unsaturation, as well as polar and acidic head groups that show a very good reproduction of structural membrane determinants, as areas per lipid, thickness, order parameter, etc., and their dependence with temperature. Simulation of membrane proteins showed unprecedented accuracy in the unbiased description of the thickness-dependent membrane-protein orientation in systems where this information is experimentally available (namely, the SarcoEndoplasmic Reticulum Calcium –SERCA-pump and its regulator Phospholamban). The interactions that lead to this faithful reproduction can be traced down to single amino acid-lipid interaction level and show full agreement with biochemical data present in the literature. Finally, the present parameterization is implemented in the GROMACS and AMBER simulation packages facilitating its use to a wide portion of the Biocomputing community.