MOLECULAR DOCKING STUDIES OF MONOMERIC WILDTYPE AND MUTANT (H81A, H49R) SOD1 WITH EDARAVONE AND RILUZOLE

RADHIKA NAGRE; VAEESHNAVI BUWA

doi:10.22159/ijcr.2022v6i4.207

Authors

RADHIKA NAGRE Department of Biochemistry, Osmania University, India
VAEESHNAVI BUWA Bioinformatics Associate, BioNome, Bangalore, India

DOI:

https://doi.org/10.22159/ijcr.2022v6i4.207

Keywords:

Amyotrophic lateral sclerosis (ALS), Cu-Zn superoxide dismutase1 (SOD1), Edaravone, Riluzole, Molecular docking

Abstract

Objective: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive loss of the upper and lower motor neurons in the brain and spinal cord. SOD1 was the first gene linked to ALS, in which more than 150 mutations throughout the sequence of the protein have been found to be associated with ALS.

Methods: The drugs that can interact and inhibit the misfolding or revert the misconformation of the protein can be useful in the treatment of ALS. Monomer apo SOD1-WT and MBR SOD1 mutants (H81A, H49R) were docked with the only two FDA-approved drugs for ALS that are edaravone and riluzole to assess if the ALS patients carrying these particular protein aggregates will derive any therapeutic efficacy.

Results: The drugs were found to interact with both wild-type and mutant SOD1 at different positions and the type of interaction, degree of interaction and their binding energies were determined. SOD1-WT has hydrophobic interactions at V103, H110, and R115 and hydrogen bond at H110 with edaravone. SOD1-WT has hydrophobic interactions at T54, F64 and hydrogen bond at D52, T58 with riluzole. Both SOD1 mutants has a hydrogen bond at its H46 residue for both drugs. SOD1-H49R mutant has hydrophobic interactions at F45 with riluzole. SOD1-H81A mutant has hydrophobic interactions at F45 with edaravone.

Conclusion: Both the mutants L42A residue has a hydrophobic interaction with edaravone. Interaction of drugs with protein and its mutants may make it possible to restore the stability of SOD1 structure and attenuate disease progression in ALS patients carrying these mutations.

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