In Silico Study of Aptamer Specificity for Detection of Insulin as Development for Diabetes Mellitus Diagnosis

https://doi.org/10.22146/ijc.91602

Dinda Exelsa Mulyani(1), Iman Permana Maksum(2*), Muhammad Yusuf(3)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, Indonesia
(*) Corresponding Author

Abstract


Diabetes mellitus (DM) is a metabolic disorder characterized by elevated blood glucose levels. There are 2 types of DM where molecular-level diagnosis becomes very important because both have different treatments to avoid treatment errors. An electrochemical aptasensor as a type 2 DM detector with insulin target has been developed. This study aims to determine the interaction and specificity based on the values of RMSD, RMSF, and binding energy between aptamer and insulin when it reaches stability in silico compared to HbA1c and glucose. Docking simulations were performed on the HDOCK webserver and dynamics simulations for 1000 ns on the aptamer and protein molecular models used. The simulation results were analyzed to see the stability and visualized using VMD to see the conformation of the aptamer-ligand complex. The docking result showed higher binding energy between aptamer-insulin compared to other molecules, namely −221.87 kcal/mol. The results of RMSF and RMSD analysis of molecular dynamics simulations show that the system is stable, has the best binding energy value of −9.9510 kcal/mol. The aptamer complex with insulin showed better specificity compared to glucose and HbA1c based on RMSD, RMSF, and binding energy.

Keywords


diabetes mellitus; aptasensor; insulin

Full Text:

Full Text PDF


References

[1] Liu, S., Shen, Z., Deng, L., and Liu, G., 2022, Smartphone assisted portable biochip for non-invasive simultaneous monitoring of glucose and insulin towards precise diagnosis of prediabetes/diabetes, Biosens. Bioelectron., 209, 114251.

[2] International Diabetes Federation, 2021, IDF Diabetes Atlas, 10th Ed., International Diabetes Federation, Brussels, Belgium.

[3] Kahanovitz, L., Sluss, P.M., and Russell, S.J., 2017, Type 1 diabetes - A clinical perspective, Point Care, 16 (1), 37–40.

[4] Zaccardi, F., Webb, D.R., Yates, T., and Davies, M.J., 2016, Pathophysiology of type 1 and type 2 diabetes mellitus: A 90-year perspective, Postgrad. Med. J., 92 (1084), 63–69.

[5] Priatna, A.S., Fadil, R.M.R., and Susanto, N.H., 2017, Blood glucose level and HbA1C in pediatric patients with diabetes mellitus type 1, Althea Med. J., 4 (2), 217–220.

[6] American Diabetes Association Professional Practice Committee, 2021, Classification and diagnosis of diabetes: Standards of medical care in diabetes-2022, Diabetes Care, 45 (Suppl. 1), S17–S38.

[7] International Expert Committee, 2009, International expert committee report on the role of the A1C assay in the diagnosis of diabetes, Diabetes Care, 32 (7), 1327–1334.

[8] Fargion, S., Dongiovanni, P., Guzzo, A., Colombo, S., Valenti, L., and Fracanzani, A.L., 2005, Iron and insulin resistance, Aliment. Pharmacol. Ther., 22 (S2), 61–63.

[9] Luong, A.D., Roy, I., Malhotra, B.D., and Luong, J.H.T., 2021, Analytical and biosensing platforms for insulin: A review, Sens. Actuators Rep., 3, 100028.

[10] Gorai, B., and Vashisth, H., 2022, Progress in simulation studies of insulin structure and function, Front. Endocrinol., 13, 908724.

[11] Radi, A.E., and Abd-Ellatief, M.R., 2021, Electrochemical aptasensors: Current status and future perspectives, Diagnostics, 11 (1), 104.

[12] Villalonga, A., Pérez-Calabuig, A.M., and Villalonga, R., 2020, Electrochemical biosensors based on nucleic acid aptamers, Anal. Bioanal. Chem., 412 (1), 55–72.

[13] Mulyani, D.E., and Maksum, I.P., 2023, Detection of biomarker using aptasensors to determine the type of diabetes, Diagnostics, 13 (12), 2035.

[14] Anand, A., Chen, C.Y., Chen, T.H., Liu, Y.C., Sheu, S.Y., and Chen, Y.T., 2021, Detecting glycated hemoglobin in human blood samples using a transistor-based nanoelectronic aptasensor, Nano Today, 41, 101294.

[15] Mulyani, R., Yumna, N., Maksum, I.P., Subroto, T., and Hartati, Y.W., 2022, Optimization of aptamer-based electrochemical biosensor for ATP detection using screen-printed carbon electrode/gold nanoparticles (SPCE/AuNP), Indones. J. Chem., 22 (5), 1256–1268.

[16] Rustaman, R., Rafi Rahmawan, R., and Maksum, I.P., 2023, In silico study of aptamer specificity for detection of adenosine triphosphate (ATP) as biosensor development for mitochondria diabetes diagnosis, Turk. Comput. Theor. Chem., 7 (2), 58–69.

[17] Zhang, D., Ma, J., Meng, X., Xu, Z., Zhang, J., Fang, Y., and Guo, Y., 2019, Electrochemical aptamer-based microsensor for real-time monitoring of adenosine in vivo, Anal. Chim. Acta, 1076, 55–63.

[18] Abrantes, M., Rodrigues, D., Domingues, T., Nemala, S.S., Monteiro, P., Borme, J., Alpuim, P., and Jacinto, L., 2022, Ultrasensitive dopamine detection with graphene aptasensor multitransistor arrays, J. Nanobiotechnol., 20 (1), 495.

[19] Kubo, I., and Eguchi, T., 2015, Study on electrochemical insulin sensing utilizing a DNA aptamer-immobilized gold electrode, Materials, 8 (8), 4710–4719.

[20] Yoshida, W., Mochizuki, E., Takase, M., Hasegawa, H., Morita, Y., Yamazaki, H., Sode, K., and Ikebukuro, K., 2009, Selection of DNA aptamers against insulin and construction of an aptameric enzyme subunit for insulin sensing, Biosens. Bioelectron., 24 (5), 1116–1120.

[21] Zeng, X., Wang, H., Zeng, Y., Yang, Y., Zhang, Z., and Li, L., 2023, Label-free aptasensor for the ultrasensitive detection of insulin via a synergistic fluorescent turn-on strategy based on G-quadruplex and AIEgens, J. Fluoresc., 33 (3), 955–963.

[22] Zhao, M., Liao, L., Wu, M., Lin, Y., Xiao, X., and Nie, C., 2012, Double-receptor sandwich supramolecule sensing method for the determination of ATP based on uranyl–salophen complex and aptamer, Biosens. Bioelectron., 34 (1), 106–111.

[23] Asadpour, F., Mazloum-Ardakani, M., Hoseynidokht, F., and Moshtaghioun, S.M., 2021, In situ monitoring of gating approach on mesoporous silica nanoparticles thin-film generated by the EASA method for electrochemical detection of insulin, Biosens. Bioelectron., 180, 113124.

[24] Pertiwi, W., Muharram, L.H., and Maulana, F.A., 2022, Prediksi struktur 3D L-asparaginase bakteri laut Vibrio sp. AND4 dengan metode homology modelling, JSFK, 9 (2), 121–128.



DOI: https://doi.org/10.22146/ijc.91602

Article Metrics

Abstract views : 2364 | views : 1075


Copyright (c) 2024 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.