Molecular docking and molecular dynamics study of 3-hydroxybutyrate

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J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 822-836, Sep-Oct 2024. DOI: https://doi.org/10.56499/jppres23.1926_12.5.822 Original Article Molecular docking and molecular dynamics study of 3-hydroxybutyrate with polymers for diabetic ketoacidosis-targeted molecularly imprinted polymers [Estudio de acoplamiento molecular y dinámica molecular de 3-hidroxibutirato con polímeros para polímeros de impresión molecular dirigidos a cetoacidosis diabética] Aiyi Asnawi1*, Ellin … Continue reading Molecular docking and molecular dynamics study of 3-hydroxybutyrate

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 822-836, Sep-Oct 2024.

DOI: https://doi.org/10.56499/jppres23.1926_12.5.822

Original Article

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

[Estudio de acoplamiento molecular y dinámica molecular de 3-hidroxibutirato con polímeros para polímeros de impresión molecular dirigidos a cetoacidosis diabética]

Aiyi Asnawi1*, Ellin Febrina2, Widhya Aligita1, La Ode Aman3, Fachrul Razi4

1Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung 40617, Indonesia.

2Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor 45363, Indonesia.

3Department of Pharmacy, Universitas Negeri Gorontalo, Jl. Jend. Sudirman No.6, Dulalowo Tim., Kec. Kota Tengah, Kota Gorontalo, Gorontalo 96128, Indonesia.

4Chemical Engineering Department, Universitas Syiah Kuala, Jl. Tgk. Syech Abdul Rauf No. 7, Darussalam-Banda Aceh 23111, Indonesia.

*E-mail: aiyi.asnawi@bku.ac.id

Abstract

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.

Keywords: 3-hydroxybutyrate; diabetic ketoacidosis; interaction; molecularly imprinted polymers; polymer.

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Resumen

Contexto: Los polímeros impresos molecularmente (MIPs) son materiales prometedores con sitios de unión a medida que pueden reconocer y unir selectivamente moléculas diana. El enfoque combinado de acoplamiento molecular y simulación de dinámica molecular (MD) proporciona información valiosa sobre las interacciones entre el 3-hidroxibutirato (3HB) y los MIPs diseñados, arrojando luz sobre los intrincados detalles de sus mecanismos de unión. Esta información es crucial para diseñar PIM con alta selectividad y afinidad por el 3HB, que es un biomarcador clave de la cetoacidosis diabética (CAD).

Objetivos: Examinar las interacciones y el comportamiento dinámico de la 3HB en un complejo con diez polímeros mediante docking molecular y simulaciones MD.

Métodos: Inicialmente, se empleó docking molecular para predecir las orientaciones y afinidades de unión de la molécula de 3HB dentro de los sitios activos de los polímeros. Posteriormente, se utilizó la simulación de dinámica molecular para explorar el comportamiento dinámico, la estabilidad y las interacciones dentro de estos complejos durante 100 ns. También se predijeron las propiedades metabólicas y toxicológicas del 3HB mediante SwissADME.

Resultados: La N-(hidroximetil)acrilamida (NHMAm), el hidroxietil metacrilato (HEMA), el ácido itacónico (ITA) y la N-[tris(hidroximetil)metil]acrilamida (TrisNHMAm) mostraron las interacciones más fuertes con el 3HB, con afinidades de unión de -2,64, 2,523, 2,469 y 2,305 kcal/mol, respectivamente. Varios tipos de interacciones moleculares influyen en la unión ligando-polímero de diversas maneras, como ilustran los cuatro polímeros con las afinidades de unión más bajas. En dinámica molecular, la 4-vinilpiridina (4VP), la N,N-dimetilacilamida (DMAm), la N-(hidroxietil)acrilamida (NHEAm) y el metacrilato de hidroxietilo (HEMA) sugieren un fuerte complejo estable con el 3HB con un ΔTOTAL global de -0,56, -0,35, -0,32 y -0,27 kcal/mol, respectivamente. La predicción ADME indicó que el 3HB tiene propiedades farmacocinéticas favorables.

Conclusiones: HEMA muestra la capacidad de interaccionar bien con 3HB tanto por acoplamiento molecular como por dinámica molecular.

Palabras Clave: 3-hidroxibutirato; cetoacidosis diabética; interacción; polímeros molecularmente impresos; polímeros.

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Citation Format: Asnawi A, Febrina E, Aligita W, Aman LO, Razi F (2024) Molecular docking and molecular dynamics study of 3-hydroxybutyrate with polymers for diabetic ketoacidosis-targeted molecularly imprinted polymers. J Pharm Pharmacogn Res 12(5): 822–836. https://doi.org/10.56499/jppres23.1926_12.5.822
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