INVESTIGADORES
CAPANI Francisco
artículos
Título:
In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium
Autor/es:
OMAR SIERRA BELLO A, JANNETH GONZALEZ A, FRANCISCO CAPANI B, GEORGE E. BARRETO
Revista:
JOURNAL OF THEORETICAL BIOLOGY
Editorial:
ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2012 vol. 315 p. 53 - 63
ISSN:
0022-5193
Resumen:
Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder characterized mainly by a
progressive loss of motor neurons. Glutamate excitotoxicity is likely the main cause of neuronal death, and
Riluzole interferes with glutamate-mediated transmission. Thus, in such independent pathway, these
effects may be partly due to inactivation of voltage-dependent sodium channels. Here we predict the
structural model of the interaction and report the possible binding sites of Riluzole on Nav1.6 channel.
The docked complexes were subjected to minimization and we further investigated the key interacting
residues, binding free energies, pairing bridge determination, folding pattern, hydrogen bounding
formation, hydrophobic contacts and flexibilities. Our results demonstrate that Riluzole interacts with
the Nav1.6 channel, more specifically in the key residues TYR 1787, LEU 1843 and GLN 1799, suggesting
possible cellular implications driven by these amino acids on Riluzole?Nav1.6 interaction, which may
serve as an important output for a more specific and experimental drug design therapy against ALS.