Fat SIRAH: Coarse-Grained Phospholipids to Explore Membrane-Protein Dynamics

BARRERA, EXEQUIEL E.; MACHADO, MATÍAS R.; PANTANO, SERGIO

JOURNAL OF CHEMICAL THEORY AND COMPUTATION

AMER CHEMICAL SOC

Año: 2019

1549-9618

The 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 (CG) 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 parametrization 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 and partial unsaturation, as well as polar and acidic head groups that show a very good reproduction of structural membrane determinants, such 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 the single amino acid-lipid interaction level and show full agreement with biochemical data present in the literature. Finally, the present parametrization is implemented in the GROMACS and AMBER simulation packages facilitating its use by a wide portion of the biocomputing community.