title: Transferring the PRIMO Coarse-Grained Force Field to the Membrane Environment: Simulations of Membrane Proteins and Helix-Helix Association.
abstract: An extension of the recently developed PRIMO coarse-grained force field to membrane environments, PRIMO-M, is described. The membrane environment is modeled with the heterogeneous dielectric generalized Born (HDGB) methodology that simply replaces the standard generalized Born model in PRIMO without further parametrization. The resulting model was validated by comparing amino acid insertion free energy profiles and application in molecular dynamics simulations of membrane proteins and membrane-interacting peptides. Membrane proteins with 148-661 amino acids show stable root-mean-squared-deviations (RMSD) between 2 and 4 Å for most systems. Transmembrane helical peptides maintain helical shape and exhibit tilt angles in good agreement with experimental or other simulation data. The association of two glycophorin A (GpA) helices was simulated using replica exchange molecular dynamics simulations yielding the correct dimer structure with a crossing angle in agreement with previous studies. Finally, conformational sampling of the 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.
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: Parimal
authors.initials: P
authors.lastname: Kar
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: Srinivasa Murthy
authors.initials: SM
authors.lastname: Gopal
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Cheng
authors.affiliation: Departments of Chemistry and Biophysics, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Afra
authors.initials: A
authors.lastname: Panahi
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States ; Department of Biochemistry and Molecular Biology and Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Feig