EXPLORING BINDING AFFINITIES OF ACETOACETATE IN ACRYLAMIDE-BASED POLYMERS (PAM) FOR MOLECULARLY IMPRINTED POLYMERS (MIPS): A MOLECULAR DOCKING AND MOLECULAR DYNAMICS STUDY

AIYI ASNAWI; ELLIN FEBRINA; LA ODE AMAN; FACHRUL RAZI

doi:10.22159/ijap.2023.v15s2.19

Authors

AIYI ASNAWI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung-40617, Indonesia https://orcid.org/0000-0002-8179-0520
ELLIN FEBRINA Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor-45363, Indonesia
LA ODE AMAN Chemistry Department, Universitas Negeri Gorontalo, Jl. Jend. Sudirman No.6, Dulalowo Tim., Kec. Kota Tengah, Kota Gorontalo, Gorontalo-96128, Indonesia
FACHRUL RAZI Chemical Engineering Department, Universitas Syiah Kuala, Jl. Tgk. Syech Abdul Rauf No. 7, Darussalam-Banda Aceh-23111, Indonesia https://orcid.org/0000-0002-8179-0520

DOI:

https://doi.org/10.22159/ijap.2023.v15s2.19

Keywords:

Acetoacetate, Acrylamide-based polymers, MIPs, Molecular docking, Molecular dynamics

Abstract

Objective: Molecularly Imprinted Polymers (MIPs) have garnered significant attention as promising materials for the selective recognition of target molecules. Acetoacetate is crucial in diabetes management, especially in Type 1 diabetes and diabetic ketoacidosis (DKA), and monitoring its levels is essential for detecting potential complications. In DKA, there is a lack of insulin resistance, leading to increased production of ketone bodies, including acetoacetate. MIPs, synthetic polymers, selectively bind to target molecules like acetoacetate due to unique three-dimensional structures, which can be quantitatively measured using molecular docking and molecular dynamics simulations. The research objectives were to assess the stability of acetoacetate-MIP complexes and their impact on polyacrylamide-based polymer (PAM) using molecular docking and molecular dynamics, examining their structural and energetic stability over 100 ns.

Methods: Five acrylamide-based polymers were investigated using AutoDock Vina for molecular docking and Gromacs for molecular dynamics simulations, focusing on binding affinities, hydrogen bonds, hydrophobic interactions, and complex behaviors over 100 ns.

Results: Acetoacetate binds well to the polymers PAM2 and PAM5, with the maximum binding affinity being 2.738 and 2.49 kcal/mol, respectively. PAM1, PAM3, and PAM4 had significant binding affinities; however, PAM4 had a lesser binding affinity of-1.534 kcal/mol, making it less appropriate for acetoacetate-specific MIP applications. The molecular dynamics investigation discovered that PAM5 had the best total energy, indicating a relatively stable interaction environment.

Conclusion: The study reveals PAM5 as a promising candidate with high binding affinity and multiple hydrogen bonds with acetoacetate, providing insights for acetoacetate-specific MIP design and molecular recognition progress.

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References

Hoffman WH, Whelan SA, Lee N. Tryptophan, kynurenine pathway, and diabetic ketoacidosis in type 1 diabetes. PLOS ONE. 2021;16(7):e0254116. doi: 10.1371/journal.pone.0254116, PMID 34280211.

Vives Pi M, Rodriguez Fernandez S, Pujol Autonell I. How apoptotic β-cells direct immune response to tolerance or to autoimmune diabetes: a review. Apoptosis. 2015;20(3):263-72. doi: 10.1007/s10495-015-1090-8, PMID 25604067.

Ling HW. Why are diabetic patients still having hyperglycemia despite diet regulation, antiglycemic medication and insulin. Int J Diabetes Metab Disord. 2019;4(2):1-14.

Kolb H, Kempf K, Rohling M, Lenzen Schulte M, Schloot NC, Martin S. Ketone bodies: from enemy to friend and guardian angel. BMC Med. 2021;19(1):313. doi: 10.1186/s12916-021-02185-0, PMID 34879839.

Kumar S, Behl T, Sachdeva M, Sehgal A, Kumari S, Kumar A. Implicating the effect of ketogenic diet as a preventive measure to obesity and diabetes mellitus. Life Sci. 2021;264:118661. doi: 10.1016/j.lfs.2020.118661, PMID 33121986.

Kanikarla Marie P, Jain SK. Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes. Free Radic Biol Med. 2016;95:268-77. doi: 10.1016/j.freeradbiomed.2016.03.020, PMID 27036365.

Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999;15(6):412-26. doi: 10.1002/(sici)1520-7560(199911/12)15:6<412::aid-dmrr72>3.0.co;2-8, PMID 10634967.

Klocker AA, Phelan H, Twigg SM, Craig ME. Blood β‐hydroxybutyrate vs. urine acetoacetate testing for the prevention and management of ketoacidosis in type 1 diabetes: a systematic review. Diabet Med. 2013;30(7):818-24. doi: 10.1111/dme.12136, PMID 23330615.

Elliott S, Smith C, Cassidy D. The post-mortem relationship between beta-hydroxybutyrate (BHB), acetone and ethanol in ketoacidosis. Forensic Sci Int. 2010;198(1-3):53-7. doi: 10.1016/j.forsciint.2009.10.019, PMID 19954904.

Saasa V, Beukes M, Lemmer Y, Mwakikunga B. Blood ketone bodies and breath acetone analysis and their correlations in type 2 diabetes mellitus. Diagnostics (Basel). 2019;9(4):224. doi: 10.3390/diagnostics9040224, PMID 31861135.

BelBruno JJ. Molecularly imprinted polymers. Chem Rev. 2019;119(1):94-119. doi: 10.1021/acs.chemrev.8b00171, PMID 30246529.

Tse Sum Bui B, Mier A, Haupt K. Molecularly imprinted polymers as synthetic antibodies for protein recognition: the next generation. Small. 2023;19(13):2206453. doi: 10.1002/smll.202206453.

Caldara M, Kulpa J, Lowdon JW, Cleij TJ, Dilien H, Eersels K. Recent advances in molecularly imprinted polymers for glucose monitoring: from fundamental research to commercial application. Chemosensors. 2023;11(1):32. doi: 10.3390/chemosensors11010032.

Noviana E, Siswanto S, Budi Hastuti AAM. Advances in nanomaterial-based biosensors for determination of glycated hemoglobin. Curr Top Med Chem. 2022;22(27):2261-81. doi: 10.2174/1568026622666220915114646, PMID 36111762.

Mustafa YL, Keirouz A, Leese HS. Molecularly imprinted polymers in diagnostics: accessing analytes in biofluids. J Mater Chem B. 2022;10(37):7418-49. doi: 10.1039/d2tb00703g, PMID 35822255.

Suryana S, Mutakin RY, Rosandi Y, Hasanah AN. An update on molecularly imprinted polymer design through a computational approach to produce molecular recognition material with enhanced analytical performance. Molecules. 2021;26(7):1891. doi: 10.3390/molecules26071891, PMID 33810542.

Boukadida M, Anene A, Jaoued Grayaa N, Chevalier Y, Hbaieb S. Choice of the functional monomer of molecularly imprinted polymers: does it rely on strong acid-base or hydrogen bonding interactions? Colloids Interface Sci Commun. 2022;50:100669. doi: 10.1016/j.colcom.2022.100669.

Elaine AA, Krisyanto SI, Hasanah AN. Dual-functional monomer MIPs and their comparison to mono-functional monomer MIPs for SPE and as sensors. Polymers. 2022;14(17):3498. doi: 10.3390/polym14173498, PMID 36080573.

Nageib AM, Halim AA, Nordin AN, Ali F. Computational modelling analysis and synthesis of molecularly imprinted polymers (MIPs) with two functional monomers using bulk polymerization. Mater Today Proc. 2023.

Snyder HD, Kucukkal TG. Computational chemistry activities with avogadro and ORCA. J Chem Educ. 2021;98(4):1335-41. doi: 10.1021/acs.jchemed.0c00959.

Hisle MS, Meier MS, Toth DM. Accelerating autodock vina with containerization. In: Proceedings of the practice and experience on advanced research computing; 2018. p. 1-5. doi: 10.1145/3219104.3219154.

Asnawi A, Nedja M, Febrina E, Purwaniati P. Prediction of a stable complex of compounds in the ethanol extract of celery leaves (Apium graveolens L.) function as a VKORC1 antagonist. TJNPR. 2023 Feb 28;7(2):2362-70, doi: 10.26538/tjnpr/v7i2.10.

Asnawi A, Aman LO, Nursamsiar A, Yuliantini E, E Febrina. Molecular docking and molecular dynamic studies: screening phytochemicals of acalypha indica against braf kinase receptors for potential use in melanocytic tumours. RJC. 2022;15(2):1352-61. doi: 10.31788/RJC.2022.1526769.

Febrina E, Alamhari RK, Abdulah R, Lestari K, Levita J, Supratman U. Molecular docking and molecular dynamics studies of acalypha indica L. phytochemical constituents with caspase-3. Int J App Pharm. 2021 Dec 11:210-5. doi: 10.22159/ijap.2021.v13s4.43861.

Febrina E, Asnawi A, Abdulah R, Lestari K, Supratman U. Identification of flavonoids from acalypha indica l. (Euphorbiaceae) as caspase-3 activators using molecular docking and molecular dynamics. Int J Appl Pharm. 2022 Dec 27:162-6.

Jejurikar BL, Rohane SH. Drug designing in Discovery Studio; 2021.

Kutzner C, Kniep C, Cherian A, Nordstrom L, Grubmüller H, de Groot BL. GROMACS in the cloud: a global supercomputer to speed up alchemical drug design. J Chem Inf Model. 2022;62(7):1691-711. doi: 10.1021/acs.jcim.2c00044, PMID 35353508.

Bernardi A, Faller R, Reith D, Kirschner KN. ACPYPE update for nonuniform 1-4 scale factors: conversion of the GLYCAM06 force field from AMBER to GROMACS. Software X. 2019;10:100241. doi: 10.1016/j.softx.2019.100241.

Fileti EE, Chaudhuri P, Canuto S. Relative strength of hydrogen bond interaction in alcohol-water complexes. Chem Phys Lett. 2004;400(4-6):494-9. doi: 10.1016/j.cplett.2004.10.149.

Acelas N, Hincapie G, Guerra D, David J, Restrepo A. Structures, energies, and bonding in the water heptamer. J Chem Phys. 2013;139(4):044310. doi: 10.1063/1.4816371, PMID 23901983.

Zhang Y, Skolnick J. The protein structure prediction problem could be solved using the current PDB library. Proc Natl Acad Sci USA. 2005;102(4):1029-34. doi: 10.1073/pnas.0407152101, PMID 15653774.

Regan B, Boyle F, O’Kennedy R, Collins D. Evaluation of molecularly imprinted polymers for point-of-care testing for cardiovascular disease. Sensors (Basel). 2019;19(16):3485. doi: 10.3390/s19163485, PMID 31395843.

Sullivan MV, Dennison SR, Archontis G, Reddy SM, Hayes JM. Toward rational design of selective molecularly imprinted polymers (MIPs) for proteins: computational and experimental studies of acrylamide based polymers for myoglobin. J Phys Chem B. 2019;123(26):5432-43. doi: 10.1021/acs.jpcb.9b03091, PMID 31150581.

Berdugo Clavijo C, Scheffer G, Sen A, Gieg LM. Biodegradation of polymers used in oil and gas operations: towards enzyme biotechnology development and field application. Polymers. 2022;14(9):1871. doi: 10.3390/polym14091871, PMID 35567040.

Torres PHM, Sodero ACR, Jofily P, Silva-Jr FP. Key topics in molecular docking for drug design. Int J Mol Sci. 2019 Sep 15;20(18):4574. doi: 10.3390/ijms20184574, PMID 31540192.

Foong YW. Borotungstic acid (BWA)-polyacrylamide (PAM) solid polymer electrolytes for electrochemical capacitors. Canada: University of Toronto; 2017.

Viveiros R, Rebocho S, Casimiro T. Green strategies for molecularly imprinted polymer development. Polymers. 2018;10(3):306. doi: 10.3390/polym10030306, PMID 30966341.

Nochebuena J, Cisneros GA. Polarizable MD. QM/MM investigation of acrylamide-based leads to target the main protease of SARS-CoV-2. J Chem Phys. 2022;157(18):185101. doi: 10.1063/5.0123698, PMID 36379777.