Coarse-Grained Molecular Dynamics Simulations of SARS-CoV-2 E Protein embedded in homogeneous saturated model membranes

Coarse-grained MD simulations of the SARS-CoV-2 E protein (PDB ID: 5X29) embedded in homogeneous mono-unsaturated model membranes of varying equilibrium thickness. Lipids with 2, 3, 4, 5, or 6 beads per acyl chain were used (Martini lipids DTPC, DLPC, DPPC, DBPC, and DXPC). All simulations were performed using GROMACS 2016 and the Martini 2.2 force field. The Berendsen thermostat was set to 313 K and a semi-isotropic Berendsen barostat was set to 1 bar in both directions. The compressibility modulus in both dimensions was 3 × 10−5 bar−1 with time constant 3 ps. Electrostatics and van der Waals (vdW) were shifted with a cutoff r-value of 1.2 nm. All systems underwent 100,000 steps of steepest-descent energy minimization prior to MD simulation with a timestep of 0.025 ps. Protein backbone beads were restrained with an elastic network which bonded all backbone bead pairs within 1.4 nm of one another with force constants of 5,000 kJ mol−1 nm−1. Five replicas of each system were simulated in the NPT ensemble for 10 μs. We discarded the first half of each trajectory prior to analysis. To determine the bulk leaflet thickness t0, we performed separate 2 μs NPT simulations of membranes composed of each lipid species listed above, but without a protein embedded. We discarded the first half of each trajectory prior to analysis. Analysis performed using nougat. Figures and figure generation script included.