Molecular docking and molecular dynamics study of 3-hydroxybutyrate


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


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.



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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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.

Asnawi A, Nedja M, Febrina E, Purwaniati P (2023) Prediction of a stable complex of compounds in the ethanol extract of celery leaves (Apium graveolens L.) function as a VKORC1 antagonist. Trop J Nat Prod Res 7: 2362–2370.

Bakchi B, Krishna AD, Sreecharan E, Ganesh VBJ, Niharika M, Maharshi S, Puttagunta SB, Sigalapalli DK, Bhandare RR, Shaik AB (2022) An overview on applications of SwissADME web tool in the design and development of anticancer, antitubercular and antimicrobial agents: A medicinal chemist’s perspective. J Mol Struct 1259: 132712.

Bernardi A, Faller R, Reith D, Kirschner KN (2019) ACPYPE update for nonuniform 1–4 scale factors: Conversion of the GLYCAM06 force field from AMBER to GROMACS. SoftwareX 10: 100241.

Brylinski M (2018) Aromatic interactions at the ligand–protein interface: Implications for the development of docking scoring functions. Chem Biol Drug Des 91: 380–390.

Butt SS, Badshah Y, Shabbir M, Rafiq M (2020) Molecular docking using chimera and autodock vina software for nonbioinformaticians. JMIR Bioinform Biotech 1: e14232.

Caldara M, Kulpa J, Lowdon JW, Cleij TJ, Diliën H, Eersels K, Grinsven Bv (2023) Recent advances in molecularly imprinted polymers for glucose monitoring: From fundamental research to commercial application. Chemosensors 11: 32.

Dhatariya KK, Glaser NS, Codner E, Umpierrez GE (2020) Diabetic ketoacidosis. Nat Rev Dis Primers 6: 40.

Elsonbaty A, Attala K, Eissa MS, Abdelshakour M, Mostafa A, Abdel Salam R, Hadad G (2023) Current advances in computer-aided design of electrochemical sensors: An analytical review. Rec Pharm Biomed Sci 7: 65–96.

Febrina E, Asnawi A (2023) Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2. J Pharm Pharmacogn Res 11: 810–822.

Gartner TEI, Jayaraman A (2019) Modeling and simulations of polymers: A roadmap. Macromolecules 52: 755–786.

Hu Y, Pan J, Zhang K, Li G (2013) Novel applications of molecularly-imprinted polymers in sample preparation. Trends Anal Chem 43: 37–52.

Karrar HR, Nouh M, Alhendi R (2022) Diabetic ketoacidosis: a review article. World Fam Med 20: 66–71.

Kryscio DR, Shi Y, Ren P, Peppas NA (2011) Molecular docking simulations for macromolecularly imprinted polymers. Ind Eng Chem Res 50: 13877–13884.

Kutzner C, Kniep C, Cherian A, Nordstrom L, Grubmüller H, de Groot BL, Gapsys V (2022) GROMACS in the cloud: A global supercomputer to speed up alchemical drug design. J Chem Inf Model 62: 1691–1711.

Liu Z, Xu Z, Wang D, Yang Y, Duan Y, Ma L, Lin T, Liu H (2021) A review on molecularly imprinted polymers preparation by computational simulation-aided methods. Polymers 13: 2657.

Martín-Esteban A (2013) Molecularly-imprinted polymers as a versatile, highly selective tool in sample preparation. Trends Anal Chem 45: 169–181.

Martín-Esteban A (2009) Molecularly imprinted polymers: Providing selectivity to sample preparation. J Chromatogr Sci 47: 254–256.

Nicholls IA, Golker K, Wiklander JG (2022) Molecular Dynamics in the Study and Development of Molecularly Imprinted Materials–Status Quo, Quo Vadis? Preprints 2022020154.

Olsson GD, Wiklander JG, Nicholls IA (2021) Using molecular dynamics in the study of molecularly imprinted polymers. Methods Mol Biol 2359: 241–268.

Ooi E, Nash K, Rengarajan L, Melson E, Thomas L, Johnson A, Zhou D, Wallett L, Ghosh S, Narendran P, Kempegowda P (2021) Clinical and biochemical profile of 786 sequential episodes of diabetic ketoacidosis in adults with type 1 and type 2 diabetes mellitus. BMJ Open Diabetes Res Care 9: e002451.

O’Reilly JE, Blackbourn LA, Caparrotta TM, Jeyam A, Kennon B, Leese GP, Lindsay RS, McCrimmon RJ, McGurnaghan SJ, McKeigue PM, McKnight JA, Petrie JR, Philip S, Sattar N, Wild SH, Colhoun HM (2020) Time trends in deaths before age 50 years in people with type 1 diabetes: a nationwide analysis from Scotland 2004–2017. Diabetologia 63: 1626–1636.

Patil R, Das S, Stanley A, Yadav L, Sudhakar A, Varma AK (2010) Optimized hydrophobic interactions and hydrogen bonding at the target-ligand interface leads the pathways of drug-designing. PloS One 5: e12029.

Peters AL, Henry RR, Thakkar P, Tong C, Alba M (2016) Diabetic ketoacidosis with canagliflozin, a sodium–glucose cotransporter 2 inhibitor, in patients with type 1 diabetes. Diabetes Care 39: 532–538.

Ramphul K, Joynauth J (2020) An update on the incidence and burden of diabetic ketoacidosis in the US. Diabetes Care 43: e196–e197.

Seong H, Lee H-B, Park K (2002) Glucose binding to molecularly imprinted polymers. J Biomater Sci Polym Ed 13: 637–649.

Snyder HD, Kucukkal TG (2021) Computational chemistry activities with Avogadro and ORCA. J Chem Educ 98: 1335–1341.

Vanelli M, Chiari G, Capuano C, Iovane B, Bernardini A, Giacalone T (2003) The direct measurement of 3-beta-hydroxy butyrate enhances the management of diabetic ketoacidosis in children and reduces time and costs of treatment. Diabetes Nutr Metab 16: 312–316.

Wallace T, Meston N, Gardner S, Matthews D (2001) The hospital and home use of a 30‐second hand‐held blood ketone meter: Guidelines for clinical practice. Diabet Med 18: 640–645.

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