Molecular dynamics simulation methods

Model SWCNTs were constructed with a (12, 12) wrapping topology to produce tubes with lengths of 7.0 nm (1340 carbon atoms) and diameters of 1.6 nm featuring armchair configurations. All coordinates for SWCNTs were generated using VMD (Visual Molecular Dynamics), and all CNT carbon atoms were assigned uncharged Lennard-Jones parameters of ε_cc = 0.36 kJ/mol and σ_cc = 3.4 Å. The c-SWCNTs included 11 carboxyl groups to mimic the relatively low carboxyl group concentration, with a total of 11 negative charges, mostly located at the two edges of the c-SWCNT. The crystal structure of human microsomal CYP3A4 (PDB ID: 1TQN) was used to initialize all protein configurations. Model 1, 2, 3, and 4 each contained one c-SWCNT and one CYP3A4 molecule placed in different initial configurations; the systems included 68.131, 78.748 and 100.969, and 98.596 atoms, respectively. All simulations were carried out on a Linux cluster using the software GROMACS (version 4.6.6) with the CHARMM 27 force field. The v-rescale thermostat and Parrinello-Rahman pressure coupling scheme were used to set the temperature and pressure at constant to 300K and 1 bar, respectively. Particle Mesh Ewald (PME) was employed to compute long-range electrostatic interactions and the cut-off for treating the van der Waals interactions was set to 10 Å. The TIP3P water model was used in all simulations and the c-SWCNT was constrained during the whole trajectory.