3.7 Possible location of bound riluzole.
To gain insights into the possible binding sites of riluzole, we performed in silico docking of this small molecule to the wild type and mutant Nav1.4 structures. The human Nav1.4 (PDB ID: 6AGF) was used, since in silico docking is more reliable to experimental structures than to homology models. Importantly, riluzole binding was not observed in the pore region or close to the pore in the central cavity in either the wild type or the F1586A (F1579A in rNav1.4) structures (Fig. 7). This inhibitor bound among transmembrane helices in three fenestrations of the wild type structure. In all cases, interactions involved the aromatic side chain of phenylalanine residues (F436, F1284, and F1586; which correspond to F430, F1277, and F1579 in rNav1.4), which are shown in Fig. 7. In the absence of the phenylalanine side chain in the F1586A mutant, only two binding sites were observed at F436 and F1284.