Molecular docking and molecular dynamics study of 3-hydroxybutyrate with polymers for diabetic ketoacidosis-targeted molecularly imprinted polymers

Context: Molecularly imprinted polymers (MIPs) are promising materials with tailored binding sites that can selectively recognize and bind target molecules. The combined approach of molecular docking and molecular dynamics (MD) simulation provides valuable insights into the interactions between 3-hydroxybutyrate (3HB) and the designed MIPs, shedding light on the intricate details of their binding mechanisms. This information is crucial for designing MIPs with high selectivity and affinity for 3HB, which is a key biomarker of diabetic ketoacidosis (DKA). Aims: To examine the interactions and dynamic behavior of 3HB in a complex with ten polymers by employing molecular docking and MD simulations. Methods: Initially, molecular docking was employed to predict the binding orientations and affinities of the 3HB molecule within the active sites of the polymers. Subsequently, molecular dynamics simulation was utilized to explore the dynamic behavior, stability, and interactions within these complexes for 100 ns. Metabolic and toxicological properties of 3HB using SwissADME were also predicted. Results: N-(hydroxymethyl)acrylamide (NHMAm), hydroxyethyl methacrylate (HEMA), itaconic acid (ITA), and N-[tris(hydroxymethyl)methyl]acrylamide (TrisNHMAm) displayed the strongest interactions with 3HB, with binding affinities of -2.64, 2.523, 2.469, and 2.305 kcal/mol, respectively. Various kinds of molecular interactions influence ligand-polymer binding in a variety of ways, as illustrated by the four polymers with the lowest binding affinities. In molecular dynamics, 4-vinylpyridine (4VP), N,N-dimethylacylamide (DMAm), N-(hydroxyethyl)acrylamide (NHEAm), and hydroxyethyl methacrylate (HEMA) suggest a strong stable complex with 3HB with an overall ΔTOTAL of -0.56, -0.35, -0.32, and -0.27 kcal/mol, respectively. The ADME prediction indicated that 3HB has favorable pharmacokinetic properties. Conclusions: HEMA shows the ability to interact well with 3HB both by molecular docking and molecular dynamics.