2.9 Structural models and in silico docking
The human Nav1.4 (PDB ID: 6AGF) was used, since in silico docking
is more reliable to experimental structures than to homology models. The
F1586A mutant structure was prepared manually by removing atoms of Phe
and renaming the residue to Ala. The protein and riluzole (ZINC database
ID: ZINC26671469) structures were prepared using prepare_ligand4.py and
prepare_receptor4.py scripts from MGLTools with default options except
hydrogens were added in the case of the protein
(https://ccsb.scripps.edu/mgltools). Riluzole was docked to the wild
type and F1586A mutant structures using Autodock Vina (Trott & Olson,
2010). The search space was set up in PyMOL (The PyMOL Molecular
Graphics System, Version 2.4, Schrödinger, LLC.) via the Autodock/Vina
plugin (Seeliger & de Groot, 2010) (supporting information Fig. S4).
The exhaustiveness option of Vina was set 128 instead of the default 8
for increasing the probability of finding the minimum of the scoring
function. The num_modes and energy_range options were set to 100 and
20, respectively, to output a higher number of docked poses.