Searching potential GSK-3β inhibitors from marine sources using atomistic simulations.

Glycogen synthase kinase-3 beta, GSK-3β, is one of the most common targets for cancer treatment. Inhibiting the biological activity of the enzyme can lead to the prevention of cancer development. Especially, estimating a new inhibitor for preventing GSK-3β by using natural compounds is of great interest. In this context, the marine compounds were investigated for their ligand-binding affinity to GSK-3β via atomistic simulations. The compounds, including xanalteric acid I, chaunolidone A, macrolactin V, and aspergiolide A, were suggested that can inhibit GSK-3β via molecular docking and steered-MD simulations. Moreover, the potency of these compounds was also confirmed via the perturbation simulations. Furthermore, the toxicity prediction also indicates that these compounds would adopt less toxicity. Therefore, it may be argued that four compounds can play as potential inhibitors preventing GSK-3β. In addition, the residues including Ile62, Val135, Pro136, Arg141, Lys183, Gln185, Asn186, and Asp200 play a crucial role in the GSK-3β binding process.