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Phosphoglycerate kinase-1 (PGK1) is an enzyme found in the cells and tissues of the human body. Deficiency of this enzyme leads to deadly neurodegenerative diseases, such as stroke, amyotrophic lateral sclerosis (ALS), Parkinson’s disease and apoptosis. Since there is no ideal drug candidate to cure such diseases by activating this enzyme, this study aimed to discover a new potent candidate from cyanobacteria using in silico pharmacological applications. The preparation of both the protein and the ligands was performed in Maestro 13.2, followed by docking using a range of modules, including Prepwizard, Ligprep, Sitemap, Glidgrid and Glide Dock, with different modes, such as HTVS, SP, XP and Desmond v6.8. Among the 240 docked cyanobacterial metabolites, lyngbyastatin, hoiamide D, lyngbyastatin 4, lyngbyastatin I, lyngbyastatin 7, tigicamide A, hoiamide and symlocamid A, showed remarkable docking and energy values. These compounds exhibit better potency as promising drugs at the target residues than reference molecules, as evidenced by better docking scores, energies, lower root mean square deviation (RMSD) with stronger binding affinities in molecular docking and MD simulations. The study demonstrated that these compounds are the first to be identified as triggers of PGK1, and it was anticipated that these metabolites would show beneficial effects when tested in both in vitro and in vivo studies of such deadly neurodegenerative diseases. The results obtained in the study suggested that these metabolites may provide a beneficial drug effect to reduce the complications associated with PGK1.
Prabhu et al. (Fri,) studied this question.