Title:Modeling Molecular Study between SDO1/Inhibitors: Search of New Treatments for Amyotrophic Lateral Sclerosis
Volume: 21
Issue: 10
Author(s): Daiana Teixeira Mancini*, Isabela Aparecida Militani, Alexandre Alves de Castro, Letícia Cristina Assis and Teodorico de Castro Ramalho
Affiliation:
- Department of Chemistry, Federal University of Lavras, Molecular Modeling Laboratory, Lavras/MG, 37200-000, Brazil
Keywords:
Theoretical study, SOD1 mutant inhibition, neurodegenerative diseases, docking, SBVS, molecular dynamics.
Abstract:
Background: The Amyotrophic lateral sclerosis (ALS) is a degenerative and most frequent
motor neuron disease characterized by the progressive impairment of upper and lower motor neurons. The
treatment of the disease is still palliative and limited to the use of only two drugs, riluzole and edaravone,
which only prolong survival by a few months. Taking into account the low number of therapy available
for this disease, identification of novel therapeutic strategies for ALS is urgently needed. The superoxide
dismutase 1 (SOD1) was the first gene in which mutations were found to be causative for the neurodegenerative
disease and has been used as a promising target for the ALS treatment.
Methods: In this work we used powerful computational tools (in silico method) such as Ligand-based
Virtual Screening (SBVS), docking and molecular dynamics techniques to collaborate with the discovery
of new candidates for more potent drugs to be used in the ALS disease treatment.
Results: Compound 1 shows good stability in the active site of the SOD1 enzyme, with an intermolecular
interaction energy of -154.80 kcal/mol. In addition, the presence of some amino acids such as Glu24,
Glu21, Pro28, Lys23 and Lys30 is important for to maintain stability of this compound inside SOD1.
Conclusion: This study was essential due to a low number of therapy available for this disease until the
moment. With this study, it was possible to observe that Compound 1 is the most promising for the design
of SOD1 mutant enzyme potential inhibitors. However, experimental tests in the SOD1 mutant to validate
the inhibitory effect of Compound 1 will be required.
