In silico modeling of emodin’s interactions with serine/threonine kinases and chitosan derivatives

(1) Lynbrook High School, San Jose, California, (2) Dougherty Valley High School, San Ramon, California, (3) Irvington High School, Fremont, California, (4) Washington High School, Fremont, California, (5) Mission San Jose High School, Fremont, California, (6) Department of Chemistry, Biochemistry, and Physical Science, Aspiring Scholars Directed Research Program, California
Cover photo for <i>In silico</i> modeling of emodin’s interactions with serine/threonine kinases and chitosan derivatives

Natural products are quickly gaining relevance as effective anticancer agents, and one example, emodin, possesses inhibitory activity against a broad spectrum of kinases, regulatory enzymes that control biological activity via phosphorylation of other molecules. Herein, through protein-ligand docking, we investigated the effect of the interaction of emodin with serine/threonine kinases, a subclass of kinases that is overexpressed in many cancers, which is implicated in phosphorylation cascades. These cascades act as intracellular messaging systems, and in the case of cancer, modify protein expression in the cell to essentially make it immortal. Thus, competitive inhibition by emodin can reduce the expression of a wide range of proteins required for essential cell function, resulting in cell death. Because the majority of serine/threonine kinases have similar active sites, we have successfully created a blueprint for emodin binding and interactions with active site residues, which include many hydrophobic interactions and minimal amounts of hydrogen bonding. Through molecular dynamics we found that emodin forms favorable interactions with chitosan and chitosan PEG (polyethylene glycol) copolymers, which could aid in loading drugs into nanoparticles (NPs) for targeted delivery to cancerous tissue. Both polymers demonstrated reasonable entrapment efficiencies, which encourages experimental exploration of emodin through targeted drug delivery vehicles and their anticancer activity.

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