Molecular Dynamics and Docking Investigation of Flavonol Aglycones against Sulfonylurea Receptor 1 (SUR1) for Anti–diabetic Drug Design

Author:

Oluwafisayo Akintemi Eric1ORCID,Kuben Govender Krishna23ORCID,Singh Thishana1ORCID

Affiliation:

1. School of Chemistry and Physics University of KwaZulu-Natal P.M.B. X54001 Durban 4000 South Africa

2. Department of Chemical Sciences University of Johannesburg, Doornfontein Campus P.O. Box. 17011 2028 Johannesburg South Africa.

3. The National Institute for Theoretical and Computational Sciences (NITheCS) South Africa

Abstract

AbstractThe effectiveness of flavonols for the treatment of certain health conditions has highlighted their importance as an alternative to conventional therapeutic drugs. In this study, fifteen (15) flavonol aglycones (no sugar moiety) were investigated against ABC transporter sulfonylurea receptor 1 (SUR1) which regulates insulin secretion in pancreatic β‐cells to maintain glucose homeostasis. Molecular docking and molecular dynamics simulations were used to examine the molecular interactions of SUR1 with selected flavonols. The binding free energies of the ligand–receptor complexes were also investigated. Important residual interactions involving the SER595, SER599, ILE423, GLN427, ALA422, ASN426, and TRP430 amino acid residues were revealed using hydrogen bonding analysis. These residues contribute to the organization for distinct folding and selectivity at the ligand–receptor interface. Selected flavonols had reasonable binding free energies with SUR1 demonstrating their potential to be considered candidates for anti–diabetic drug design.

Publisher

Wiley

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