PRIMO-M: An Extension of the Coarse-Grained Force Field Primo to the Membrane Environment

Abstract

CG models for biomolecules and lipids are widely established but often suffer from a lack of transferability between different systems and to different environments. Furthermore, the combination with atomistic force fields in hybrid AA/CG multiscale models is often challenging. To alleviate these problems, we have previously developed the PRIMO coarse-grained force field. Here, the extension of PRIMO to membrane environments, PRIMO-M, is presented. The membrane environment is modeled implicitly with the heterogeneous dielectric generalized Born methodology that simply replaces the standard generalized Born model in PRIMO without further parameterization. The resulting model was initially validated by reproducing amino acid insertion free energy profiles. Membrane proteins with 148-661 amino acids show stable root-mean-squared-deviation between 2 and 4 A for most systems. PRIMO-M was able to predict tilt angles of several transmembrane helical peptides that are in good agreement with experimental or other simulation data. The association of two glycophorin A helices was simulated using replica exchange molecular dynamics simulations yielding the correct dimer structure with a crossing angle in agreement with previous studies. Finally, the conformational sampling of influenza fusion peptide also generates structures in agreement with previous studies. Overall, these findings suggest that PRIMO-M can be used to study membrane bound peptides and proteins and validates the transferable nature of the PRIMO coarse-grained force field.