Evaluation of marine algal sulphated polysaccharides as Glucose 6 phosphatase catalytic subunit 1 (G6PC1) inhibitors-A computational approach

Abstract

Glucose 6-phosphatase(G6Pase), an enzyme involved in glycogenolysis and gluconeogenesis, controls glucose production and maintains blood glucose levels through its intrinsic membrane protein, Glucose 6 phosphatase catalytic subunit (G6PC1). G6PC1 inhibition despite being identified as a promising diabetes treatment strategy, effective G6PC1 inhibitors remain unrecognized in the clinical environment. The current investigation concentrates on the computational inhibition of the G6PC1 by marine algal sulphated polysaccharides (SPs). The Ramachandran plot checked the alpha-fold structure of the G6PC1 stereo chemical property through the molprobity server. This study examined 15 SPs for their potent interaction with the G6PC1 enzyme, utilizing a computational approach to identify potent antidiabetic molecules. Among the 15 SPs, drug-likeness, ADMET, and toxicity properties of fucoidan showed promising results that it is nontoxic following the drug-likeness rule. The molecular docking studies signified that fucoidan has the highest binding energy of -4.32 kJ mol^-¹ to the G6PC1 active site compared to other selected SPs. The drug control metformin showed the lowest binding energy of about -3.92 kJ mol^-¹ to the G6PC1. Further molecular dynamics simulations (MD) revealed that the G6PC1-fucoidan complex is stable, as evidenced by the root mean square deviation (RMSD), fluctuations (RMSF) and radius of gyration (Rg) graphs for 50 ns. Overall, data support the potential importance of fucoidan, which could efficiently inhibit or reduce the activity of the G6PC1 enzyme and has proven to be a good measure to control the levels of diabetes in humans; however, further in vivo and in vitro investigations are required for further validation of these results.