Page Header Logo Applied Science and Engineering Progress

Home > ONLINE FIRST > Phakeenuya

Computational Screening and Molecular Docking Analysis of Bioactive Peptides from Spent Coffee Grounds as Potential α-Glucosidase and α-Amylase Inhibitors for Antidiabetic Therapy

Vanarat Phakeenuya, Theerawut Phusantisampan, Malinee Sriariyanun

Abstract


A metabolic disease, type 2 diabetes mellitus (T2DM), is marked by chronic hyperglycemia due to insulin resistance or impaired secretion. Inhibiting carbohydrate-digesting enzymes, particularly α-glucosidase and α-amylase, is a therapeutic approach to regulate blood glucose levels. Protein components of spent coffee grounds (SCG), a byproduct of coffee production, can be hydrolyzed to produce bioactive peptides with potential health benefits. In this study, the 11S storage protein of SCG was simulated with alcalase digestion for peptide synthesis. These peptides were computationally screened for antidiabetic potential using bioactivity prediction tools and were evaluated for bioactivity, toxicity, bitterness, blood stability, and protein-binding potential. Most were predicted to be non-toxic, non-bitter, and had favorable blood half-lives (>830 s), suggesting therapeutic viability.  Molecular docking was performed against α-glucosidase and α-amylase to assess binding affinity. The amino acids TRP406, ARG526, and ASP542 of α-glucosidase were strongly bound by the peptides GRPQPRL and RRF, which had binding strengths of -8.5 and -8.3 kcal/mol, respectively. Meanwhile, ASP197, GLU233, ASP300, HIS299, and HIS305 were key components of α-amylase’s binding with APHW (-8.7 kcal/mol). The presence of aromatic and polar residues contributed to binding strength and stability in enzyme active sites. These results indicate that SCG-derived peptides have promising inhibitory activity against α-glucosidase and α-amylase and may serve as natural, safe, and stable candidates for developing functional antidiabetic therapies.

Keywords



[1]    D. Lovic, A. Piperidou, I. Zografou, H. Grassos, A. Pittaras, and A. Manolis, “The growing epidemic of diabetes mellitus,” Current Vascular Pharmacology, vol. 18, pp. 104–109, 2020.                                   

[2]    G. Danaei et al., “National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 27 million participants,” Lancet, vol. 378, pp. 31–40, 2011.

[3]    N. M. Maruthur et al., “Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: A systematic review and meta-analysis,” Annals of Internal Medicine, vol. 164, no. 11, pp. 740–751, 2016, doi: 10.7326/M15-2650.

[4]    C. J. Bailey and C. Day, “Metformin: Its botanical background,” Practical Diabetes International, vol. 28, no. 3, pp. 115–117, 2011, doi: 10.1002/pdi.1574.

[5]    K. J. Lipska et al., “National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011,” JAMA Internal Medicine, vol. 177, no. 7, pp. 1018–1025, 2017, doi: 10.1001/jamainternmed.2017.0899.

[6]    J. Robyt, “Starch: Structure, properties chemistry and enzymology,” in Glycoscience, B. O. Fraser-Reid, K. Tatsuta, and J. Thiem, Eds. Berlin, Heidelberg: Springer, 2008, pp. 1437–1472.

[7]    V. Manohar, N. A. Talpur, B. W. Echard, and S. Lieberman, H. G. Preuss, “Effects of a water soluble extract of maitake mushrooms on circulating glucose insulin concentrations in mice,” Diabetes, Obesity and Metabolism, vol. 4, pp. 370–385, 2002.

[8]    J. Wang et al., “Anti-diabetic effect by walnut (Juglans mandshurica Maxim.) derived peptide LPLLR through inhibiting-glucosidase and-amylase, and alleviating insulin resistance of hepatic HepG2 cells,” Journal of Functional Foods, vol. 69, p. 103944, 2020.

 [9]   T. Fujisawa, H. Ikegami, K. Inoue, Y. Kawabata and T. Ogihara, “Effect of two alpha-glucosidase inhibitors, voglibose and acarbose, on postprandial hyperglycemia correlates with subjective abdominal symptoms,” Metabolism, vol. 54, pp. 387–398, 2005.

[10] M. Barati et al., “Techniques, perspectives, and challenges of bioactive peptide generation: A comprehensive systematic review,” Comprehensive Reviews in Food Science and Food Safety, vol. 19, pp. 1488–1520, 2020.

[11] C. C. Udenigwe and R. E. Aluko, “Food protein-derived bioactive peptides: production, processing, and potential health benefits,” Journal of Food Science, vol. 77, no. 1, pp. R11–R24, 2012, doi: 10.1111/j.1750-3841.2011. 02455.x.

[12] A. Lemes, L. Sala, J. Ores, A. Braga, M. Egea, and K. Fernandes, “A review of the latest advances in encrypted bioactive peptides from protein-rich waste,” International Journal of Molecular Sciences, vol. 17, no. 6, p. 950, 2016, doi: 10.3390/ijms17060950.

[13] S. P. Patil, A. Goswami, K. Kalia, and A. S. Kate, “Plant-derived bioactive peptides: A treatment to cure diabetes,” International Journal of Peptide Research and Therapeutics, vol. 26, no. 2, p. 955, 2020, doi: 10.1007/ S10989-019-09899-Z.

[14] H. Lin et al., “Computational screening for novel α-glucosidase inhibitory peptides from Chlamys nobilis adductor muscle as a potential antidiabetic agent,” Frontiers in nutrition, vol. 12, p. 1566107, 2025, doi: 10.3389/fnut.2025. 1566107.

[15] P. Antony and R. Vijayan, “Bioactive peptides as potential nutraceuticals for diabetes therapy: A comprehensive review,” International Journal of Molecular Sciences, vol. 22, no. 16, p. 9059, 2021, doi: 10.3390/ijms22169059.

[16] H. Zhou, B. Safdar, H. Li, L. Yang, Z. Ying and X.  Liu, “Identification of a novel α-amylase inhibitory activity peptide from quinoa protein hydrolysate,” Food Chemistry, vol. 403, p.134434, 2023, doi: 10.1016/j.foodchem.2022. 134434.

[17] G. J. Fadimu, A. Farahnaky, H. Gill, O. A. Olalere, C.-Y Gan, and T. Truong, “In-silico analysis and antidiabetic effect of α-amylase and α-glucosidase inhibitory peptides from lupin protein hydrolysate: Enzyme-peptide interaction study using molecular docking approach,” Foods, vol. 11, no. 21, p. 3375, 2022, doi: 10.3390/foods11213375.

[18] V. G. Tacias-Pascacio, R. Morellon-Sterling, E. H. Siar, O. Tavano, Á. Berenguer-Murcia, and R. Fernandez-Lafuente, “Use of Alcalase in the production of bioactive peptides: A review,” International Journal of Biological Macromolecules, vol. 165, pp. 2143–2196, 2020, doi: 10.1016/j.ijbiomac.2020.10.060.

[19] S. T. Chen, S. Y. Chen, and K. T. Wang, “Kinetically controlled peptide bond formation in anhydrous alcohol catalyzed by the industrial protease Alcalase,” Journal of Organic Chemistry, vol. 57, pp. 6960–6965, 1992, doi: 10.1021/jo00051a052.

[20] C. H. Tran, H. Le, T. Le, and M. Phan, “Effects of enzyme types and extraction conditions on protein recovery and antioxidant properties of hydrolysed proteins derived from defatted Lemna minor,” Applied Science and Engineering Progress, vol. 10, 2021, doi: 10.14416/j.asep.2021.05.003.

[21] D. C. Nguyen, V. Le Nguyen, and H. V. H. Nguyen, “Optimization of enzyme-assisted extraction of bioactive peptides from whiteleg shrimp (Litopenaeus vannamei) head waste using Box–Behnken design,” Applied Science and Engineering Progress, vol. 17, no. 1, p. 6945, 2024, doi: 10.14416/j.asep.2023.09.002.

[22] A. S. Franca and L. S. Oliveira, “Potential uses of spent coffee grounds in the food industry,” Foods, vol. 11, no. 14, p. 2064, 2022, doi: 10.3390/foods11142064.

[23]  E. Ribeiro, T. de Souza Rocha, and S. H. Prudencio, “Potential of green and roasted coffee beans and spent coffee grounds to provide bioactive peptides,” Food Chemistry, vol. 348, p. 129061, 2021.

[24] K. Ramírez, K. V. Pineda-Hidalgo, and J. J. Rochín-Medina, “Fermentation of spent coffee grounds by Bacillus clausii induces release of potentially bioactive peptides,” LWT, vol. 138, p. 110685, 2021, doi: 10.1016/j.lwt.2020.110685.

[25] J. J. Rochín-Medina, E. S. Ramírez-Serrano, and K. Ramírez, “Inhibition of α-glucosidase activity by potential peptides derived from fermented spent coffee grounds,” Food Chemistry, vol. 454, p. 139791, 2024.

[26] A. Peredo-Lovillo, A. Hernández-Mendoza, B. Vallejo-Cordoba, and H. E. Romero-Luna, “Conventional and in silico approaches to select promising food-derived bioactive peptides: A review,” Food Chemistry: X, vol. 13, p. 100183, 2021, doi: 10.1016/j.fochx.2021.100183.

[27] D. Zhao et al., “PEP-FOLD design, synthesis, and characteristics of finger-like polypeptides,” Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy, vol. 224, p. 117401, 2019, doi: 10.1016/j.saa.2019.117401.

[28]   O. Trott and A. J. Olson, “AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading,” Journal of Computational Chemistry, vol. 31, pp. 455–461, 2010, doi: 10.1002/jcc.21334.

[29]  G. M. Morris et al., “AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility,” Journal of Computational Chemistry, vol. 30, pp. 2785–2791, 2009, doi: 10.1002/jcc.21256.

[30] J. Gasteiger and M. Marsili, “Iterative partial equalization of orbital electronegativity—A rapid access to atomic charges,” Tetrahedron, vol. 36, pp. 3219–3228, 1980, doi: 10.1016/0040-4020(80)80168-2.

[31]  E. Mateev, I. Valkova, B. Angelov, M. Georgieva, and A. Zlatkov, “Validation through re-docking, cross-docking and ligand enrichment in various well-resoluted MAO-B receptors,” International Journal of Pharmaceutical Sciences and Research, vol. 13, pp. 1099–1107, 2021.

[32] R. Acuña et al., “Coffee seeds contain 11S storage proteins,” Physiologia Plantarum, vol. 105, pp. 122–131, 1999, doi: 10.1034/j.1399-3054.1999.105119.x.

[33] N. J. Adamson and E. C. Reynolds, “Characterization of casein phosphopeptides prepared using alcalase: Determination of enzyme specificity,” Enzyme and Microbial Technology, vol. 19, no. 3, pp. 202–207, 1996, doi: 10.1016/0141-0229(95)00232-4.

[34]  H. Korhonen and A. Pihlanto, “Bioactive peptides: Production and functionality,” International Dairy Journal, vol. 16, no. 9, pp. 945–960, 2006, doi: 10.1016/j.idairyj.2005.10. 012

[35] A. B. Nongonierma and R. J. FitzGerald, “The scientific evidence for the role of milk protein-derived bioactive peptides in humans: A review,” Journal of Functional Foods, vol. 17, pp. 640–656, 2015, doi: 10.1016/j.jff.2015.06.02.

[36] M. Arnal, M. Gallego, P. Talens, and L. Mora, “Impact of thermal treatments and simulated gastrointestinal digestion on the α-amylase inhibitory activity of different legumes,” Food Chemistry, vol. 418, p. 135884, 2023, doi: 10.1016/j.foodchem.2023.135884.

[37] T. Matoba and T. Hata, “Relationship between bitterness of peptides and their constituent amino acids,” Agricultural and Biological Chemistry, vol. 36, no. 8, pp. 1423–1431, 1972, doi: 10.1080/00021369.1972.10860172.

[38] C. Mooney, N. J. Haslam, G. Pollastri, and D. C. Shields, “Towards the improved discovery and design of functional peptides: Common features of diverse classes permit generalized prediction of bioactivity,” PLoS One, vol. 7, no. 10, p. e45012, 2012, doi: 10.1371/journal.pone. 0045012.

[39] L. G. Trabuco, S. Lise, E. Petsalaki, and R. B. Russell, “PepSite: Prediction of peptide-binding sites from protein surfaces,” Nucleic Acids Research, vol. 40, no. W1, pp. W423–W427, 2012, doi: 10.1093/nar/gks398.

[40] I. Gülseren, and B. Vahapoglu, “ The stability of food bioactive peptides in blood: An overview,” International Journal of Peptide Research and Therapeutics, vol. 28, no. 2, pp. 1–7, 2022, doi: 10.1007/s10989-021-10321-w.

[41] M. Kuroda and N. Miyamura, “Studies on the relationship between bitterness of peptides and their chemical structures,” Journal of the Agricultural Chemical Society of Japan, vol. 57, pp. 879–884, 1993.

[42] S. Kumar, S. Narwal, V. Kumar, and O. Prakash, “α-Glucosidase inhibitors from plants: A natural approach to treat diabetes,” Pharmacognosy Reviews, vol. 5, no. 9, pp. 19–29, 2011, doi: 10.4103/0973-7847.79096.

[43] Y. M. Kim, Y. K. Jeong, M. H. Wang, W. Y. Lee, and H. I. Rhee, “Inhibitory effect of pine bark extract on α-glucosidase activity and postprandial hyperglycemia,” Nutrition, vol. 20, no. 8, pp. 737–741, 2010, doi: 10.1016/j.nut. 2004.03.020.

[44] J. K. Yadav and V. Prakash, “Stabilization of α-amylase, the key enzyme in carbohydrates properties alterations, at low pH,” International Journal of Food Properties, vol. 14, pp. 1182–1196, 2011.

[45] H. Yang et al., “Structure-based engineering of histidine residues in the catalytic domain of α-amylase from Bacillus subtilis for improved protein stability and catalytic efficiency under acidic conditions,” Journal of Biotechnology, vol. 164, pp. 59–66, 2013.

[46] G. Buisson, E. Duee, R. Haser, and F. Payan, “Three-dimensional structure of porcine pancreatic alpha-amylase at 2.9 Å resolution. Role of calcium in structure and activity,” EMBO Journal, vol. 6, pp. 3909–3916, 1987.

[47] E. A. MacGregor, Š. Janeček, and B. Svensson, “Relationship of sequence and structure to specificity in the α-amylase family of enzymes,” Biochimica et Biophysica Acta, vol. 1546, no. 1, pp. 1–20, 2001, doi: 10.1016/ S0167-4838(00)00212-6.

[48] X. Yu et al., “Studies on the interactions of theaflavin-3,3′-digallate with bovine serum albumin: Multi-spectroscopic analysis and molecular docking,” Food Chemistry, vol. 366, p. 130422, 2022.

[49] Nursamsiar, M. Siregar, A. Awaluddin, N. Nurnahari, S. N. E, Febrina, and A. Asnawi “Molecular docking and molecular dynamic simulation of the aglycone of curculigoside A and its derivatives as alpha glucosidase inhibitors,” RASĀYAN Journal of Chemistry, vol. 13, no. 1, pp. 690–698, 2020, doi: 10.31788/RJC.2020.1315577.

[50] O. A. Ladokun, A. Abiola, D. Okikiola, and F. Ayodeji, “GC-MS and molecular docking studies of Hunteria umbellata methanolic extract as a potent anti-diabetic,” Informatics in Medicine Unlocked, vol. 13, pp. 1–8, 2018.

[51] C. M. Ma, T. T. Liu, L. Yang, Y. G. Zu, and W. Wang, “α-Glucosidase inhibitors from natural products: A review,” Mini-Reviews in Medicinal Chemistry, vol. 11, no. 5, pp. 444–451, 2011, doi: 10.2174/138955711795305780.

[52] Y. Liu, W. Liu, H. Li, and H. Zhang, “Docking studies and QSAR modeling of α-glucosidase inhibitors for diabetes therapy,” International Journal of Molecular Sciences, vol. 20, no. 6, p. 1290, 2019, doi: 10.3390/ijms20061290.

[53] C. N. Pace et al., “Contribution of hydrogen bonds to protein stability,” Protein Science, vol. 23, no. 5, pp. 652–661, 2014, doi: 10.1002/pro. 2449.

[54] H.-L. Siow, T. S. Lim, and C.-Y. Gan, “Development of a workflow for screening and identification of α-amylase inhibitory peptides from food source using an integrated bioinformatics-phage display approach: Case study–Cumin seed,” Food Chemistry, vol. 214, pp. 67–76, 2017, doi: 10.1016/j.foodchem. 2016.07.069.

[55] Y. Zhang et al., “Preparation and identification of peptides with α-glucosidase inhibitory activity from Shiitake mushroom (Lentinus edodes) protein,” Foods, vol. 12, no. 13, p. 2534, 2023, doi: 10.3390/foods12132534.

[56] H. Zhou, B. Safdar, H. Li, L. Yang, Z. Ying, and X.  Liu, “Identification of a novel α-amylase inhibitory activity peptide from quinoa protein hydrolysate,” Food Chemistry, vol. 403, p.134434, 2023, doi: 10.1016/j.foodchem.2022. 134434.

[57] X. Tang et al., “Virtual screening technology for two novel peptides in soybean as inhibitors of α-amylase and α-glucosidase,” Foods, vol. 12, no. 24, p. 4387, 2023, doi: 10.3390/foods 12244387.

[58] M. A. Ibrahim, M. J. Bester, A. W. Neitz, and A. R. M. Gaspar, “Rational in silico design of novel α-glucosidase inhibitory peptides and in vitro evaluation of promising candidates,” Biomedicine & Pharmacotherapy, vol. 107, pp. 234–242, 2018, doi: 10.1016/j.biopha.2018. 07.163.

Full Text: PDF

DOI: 10.14416/j.asep.2025.09.002

Refbacks

  • There are currently no refbacks.


Copyright © 2025 by King Mongkut’s University of Technology North Bangkok. All rights reserved.