2.2. Molecular Dynamics

Each of the five models was inserted into a heterogeneous neuronal plasma membrane (Table 1) using the CHARMM-GUI membrane builder [19,20]. A box of 250 Å × 250 Å was established with periodic boundary conditions. The system was solvated with 150 mM NaCl at a net charge of zero using the TIP3P water model [21]. The simulations were run in GROMACS [22] using the University of Cambridge High Performance Computing Resources. Long-range electrostatic interactions were calculated using the Particle-mesh Ewald method with the Coulomb and van der Waals interaction cut-offs set to 12 Å [23]. The LINCS algorithm was used to constrain molecular bonds. All systems were run using the CHARMM36m force field. Following steepest descent minimisation, all systems were subjected to six series of a 125 picosecond NPT equilibration ensemble with temperature coupling with velocity rescaling and pressure coupling using the Parrinello–Rahman method [24,25,26] for all simulations. Simulation time steps were set at 2 fs, and, as RMSDs plateaued within 10 ns for all models, total simulation runtimes were 50 ns (receptor models) or 25 ns (docked receptor models); simulations were run 3–5 times for each model.

Lipid composition of the neuronal plasma membrane.