Cheminformatics study: Homology modeling and molecular docking simulations study on milk proteins with most drugs used in dairy sector

Paper Details

Research Paper 08/06/2024
Views (84) Download (12)
current_issue_feature_image
publication_file

Cheminformatics study: Homology modeling and molecular docking simulations study on milk proteins with most drugs used in dairy sector

Zabron Janes, Daniel Shadrack, John Kyaruzi, Hulda Swai, Gabriel Shirima
Int. J. Biosci.24( 6), 123-137, June 2024.
Certificate: IJB 2024 [Generate Certificate]

Abstract

The widespread use of drugs in agriculture and husbandry poses a significant risk to human health through direct exposure via dairy products. In this study, the effects of drug interactions on the conformation, binding modes and affinities was investigated by employing in-silico methods, including homology modeling and molecular docking. Bovine milk proteins (PDB ID: ICE2, 3GC1, 7ER3, 4F5S), and drugs (oxytetracycline CID:54675779, enrofloxacin CID:2082, penicillin, CID: 5904 and albendazole CID:71188) were sourced from the RCSB protein data bank and PubChem database, respectively. Since Bovine β-casein crystal structure is experimentally not resolved and, its structure is absent in PDB bank, homology modeling was used to construct a 3D structure.   MODELLER and I-TASSER were used to model the protein with an accuracy of 87.4% and 89.6%, respectively. Molecular docking simulations reveal that enrofloxacin and oxytetracycline, with Bovine lactoperoxidase (3GC1), showed a strong affinity of -8.4 kcal/mol and -8.3 kcal/mol, respectively. This study provides insights into molecular interactions pivotal for understanding milk quality. The implications extend to environmental, human health, and animal welfare, emphasizing the need for informed strategies in the dairy sector and in pharmaceutical industries during drug design and development.

VIEWS 19

Attique SA, Hassan M, Usman M, Atif RM, Mahboob S, Al-Ghanim KA, Nawaz MZ. 2019. A molecular docking approach to evaluate the pharmacological properties of natural and synthetic treatment candidates for use against hypertension. International Journal of Environmental Research and Public Health 16(6), 923.

Azabo R, Mshana S, Matee M, Kimera SI. 2022. Antimicrobial usage in cattle and poultry production in Dar es Salaam, Tanzania: pattern and quantity. BMC Veterinary Research 18(1), 1–12. https://doi.org/10.1186/s12917-021-03056-9

Balivo A, d’Errico G, Genovese A. 2024. Sensory properties of foods functionalised with milk proteins. Food Hydrocolloids 147, 109301. https://doi.org/10.1016/j.foodhyd.2023.109301

Bandyopadhyay S, Joshi L. 2022. Understanding Implications of Dairy Sector Development to Sustainable Development Goals (SDGs) 139, 20220380539. New Delhi, India: National Council of Applied Economic Research.

Bianchetti L, Thompson JD, Lecompte O, Plewniak F, Poch O. 2005. vALId: Validation of protein sequence quality based on multiple alignment data. Journal of Bioinformatics and Computational Biology 3(4), 929–947. https://doi.org/10.1142/S0219720005001326

Bourassa P, Bariyanga J, Tajmir-Riahi HA. 2013. Binding sites of resveratrol, genistein, and curcumin with milk α- and β-caseins. Journal of Physical Chemistry B 117(5), 1287–1295. https://doi.org/10.1021/jp3114557

Burley SK, Bhikadiya C, Bi C, Bittrich S, Chao H, Chen L, Craig PA, Crichlow GV, Dalenberg K, Duarte JM, Dutta S, Fayazi M, Feng Z, Flatt JW, Ganesan S, Ghosh S, Goodsell DS, Green RK, Guranovic V, Zardecki C. 2023. RCSB Protein Data Bank (RCSB.org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning. Nucleic Acids Research 51(1 D), D488–D508. https://doi.org/10.1093/nar/gkac1077

Caneschi A, Bardhi A, Barbarossa A, Zaghini A. 2023. The use of antibiotics and antimicrobial resistance in veterinary medicine, a complex phenomenon: a narrative review. Antibiotics 12(3). https://doi.org/10.3390/antibiotics12030487

Chi Z, Liu R, Teng Y, Fang X, Gao C. 2010. Binding of oxytetracycline to bovine serum albumin: spectroscopic and molecular modeling investigations. Journal of Agricultural and Food Chemistry 58(18), 10262–10269. https://doi.org/10.1021/jf101417w

Dantas MD. de A, Silva M. de M, Silva ON, Franco OL, Fensterseifer ICM, Tenório H. de A, Pereira HJV, Figueiredo IM, Santos JCC. 2020. Interactions of tetracyclines with milk allergenic protein (casein): a molecular and biological approach. Journal of Biomolecular Structure and Dynamics 38(18), 5389–5400. https://doi.org/10.1080/07391102.2019.1702587

Dastmalchi S, Hamzeh-Mivehroud M, Sokouti B. 2016. Methods and algorithms for molecular docking-based drug design and discovery. IGI Global 456, 47-60.

Davoodi SH, Shahbazi R, Esmaeili S, Sohrabvandi S, Mortazavian AM, Jazayeri S, Taslimi A. 2016. Health-related aspects of milk proteins. Iranian Journal of Pharmaceutical Research 15(3), 573–591.

De Wit JN. 1998. Nutritional and functional characteristics of whey proteins in food products. Journal of Dairy Science 81(3), 597–608. https://doi.org/10.3168/jds.S0022-0302(98)75613-9

FAO, GDP, ICFN. 2018. Dairy Development’s Impact on Poverty Reduction. https://ifcndairy.org/wp-content/uploads/2018/10/IFCN

Fiser A. 2010. Template-Based Protein Structure Modeling. Methods in Molecular Biology (Clifton, N.J.) 673, 73–94. https://doi.org/10.1007/978-1-60761-842-3_6

Fox PF. 2003. Milk Proteins: General and Historical Aspects. Advanced Dairy Chemistry—1 Proteins 1, 1–48. https://doi.org/10.1007/978-1-4419-8602-3_1

Gasteiger J, Marsili M. 1978. A new model for calculating atomic charges in molecules. Tetrahedron Letters 19(34), 3181–3184. https://doi.org/10.1016/S0040-4039(01)94977-9

Gellrich K, Meyer HHD, Wiedemann S. 2014. Composition of major proteins in cow milk differing in mean protein concentration during the first 155 days of lactation and the influence of season as well as short-term restricted feeding in early and mid-lactation. Czech Journal of Animal Science 59(3), 97–106. https://doi.org/10.17221/7289-cjas

Genheden S, Reymer A, Saenz-Méndez P, Eriksson LA. 2017. Computational Chemistry and Molecular Modelling Basics. In Computational Tools for Chemical Biology. https://doi.org/10.1039/9781788010139-00001

Gohlke H, Hendlich M, Klebe G. 2000. Knowledge-based scoring function to predict protein-ligand interactions. Journal of Molecular Biology 295(2), 337–356. https://doi.org/10.1006/jmbi.1999.3371

Guntero VA, Gutierrez L, Kneeteman MN, Ferretti CA. 2021. In Silico Study of the Interaction between Casein with Tocopherols: Preliminary Evaluation of Lipophilic Substrate Inclusion on Proteic Matrix. 49. https://doi.org/10.3390/ecsoc-24-08345

Habibian-Dehkordi S, Farhadian S, Ghasemi M, Evini M. 2022. Insight into the binding behavior, structure, and thermal stability properties of β-lactoglobulin/Amoxicillin complex in a neutral environment. Food Hydrocolloids 133, 107830. https://doi.org/10.1016/j.foodhyd.2022.107830

Herrero M, Grace D, Njuki J, Johnson N, Enahoro D, Silvestri S, Rufino MC. 2013. The roles of livestock in developing countries. Animal 7(s1), 3–18. https://doi.org/10.1017/S1751731112001954

Huey R, Morris G. 2008. Using AutoDock 4 with AutoDocktools: a tutorial. The Scripps Research Institute, USA 8, 54-6. https://dasher.wustl.edu/chem478/software/autodock-tutorial.pdf

Jagadeesh T, Parthiban M, Raja P, Sarathchandra G, Vairamuthu S. 2023. in Silico and in Vitro Evaluation of Enrofloxacin on Aflatoxin B1-Induced Cytotoxicity. Exploratory Animal and Medical Research 13(2), 243–251. https://doi.org/10.52635/eamr/13.2.243-251

Jalily Hasani H, Barakat K. 2017. Homology modeling: An overview of fundamentals and tools. International Review on Modelling and Simulations 10(2), 129–145. https://doi.org/10.15866/iremos.v10i2.11412

Kalin R, Köksal Z, Bayrak S, Gerni S, Ozyürek IN, Usanmaz H, Karaman M, Atasever A, Özdemir H, Gülçin İ. 2022. Molecular docking and inhibition profiles of some antibiotics on lactoperoxidase enzyme purified from bovine milk. Journal of Biomolecular Structure and Dynamics 40(1), 401–410. https://doi.org/10.1080/07391102.2020.1814416

Kong F, Tian J, Yang M, Zheng Y, Cao X, Yue X. 2020. Characteristics of the interaction mechanisms of xylitol with β-lactoglobulin and β-casein: A multi-spectral method and docking study. Spectrochimica Acta – Part A: Molecular and Biomolecular Spectroscopy 243, 118824. https://doi.org/10.1016/j.saa.2020.118824

Kosgey A, Shitandi A, Marion JW. 2018. Antibiotic residues in milk from three popular Kenyan milk vending machines. American Journal of Tropical Medicine and Hygiene 98(5), 1520–1522. https://doi.org/10.4269/ajtmh.17-0409

Kumar A, Panda AK, Sharma N. 2022. Determination of antibiotic residues in bovine milk by HPLC-DAD and assessment of human health risks in Northwestern Himalayan region, India. Journal of Food Science and Technology 59(1), 95–104. https://doi.org/10.1007/s13197-021-04988-8

Kumar A, Sharma A, Kaur H, Punera S, Tanwar P, Kumar P. 2021. Interaction of Protein-Ligand: Molecular Docking, A Novel Computational Biology Tool. Annals of the Romanian Society for Cell Biology 25(6), 20763–20775. https://www.researchgate.net/publication/356033779

Kurjogi M, Mohammad YHI, Alghamdi S, Abdelrahman M, Satapute P, Jogaiah S. 2019. Detection and determination of stability of the antibiotic residues in cow’s milk. PLoS ONE 14(10), 1–14. https://doi.org/10.1371/journal.pone.0223475

Lemma DH, Mengistu A, Kuma T, Kuma B. 2018. Improving milk safety at farm-level in an intensive dairy production system: Relevance to smallholder dairy producers. Food Quality and Safety 2(3), 135–143. https://doi.org/10.1093/fqsafe/fyy009

Liang G, Zhao J, Gao Y, Xie T, Zhen J, Pan L, Gong W. 2024. Application and evaluation of molecular docking for aptamer and small molecular interaction – A case study with tetracycline antibiotics. Talanta 266, 124942. https://doi.org/10.1016/j.talanta.2023.124942

Makwana KM, Mahalakshmi R. 2015. Implications of aromatic-aromatic interactions: From protein structures to peptide models. Protein Science 24(12), 1920–1933. https://doi.org/10.1002/pro.2814

Maleko D, Msalya G, Mwilawa A, Pasape L, Mtei K. 2018. Smallholder dairy cattle feeding technologies and practices in Tanzania: failures, successes, challenges and prospects for sustainability. International Journal of Agricultural Sustainability 16(2), 201–213. https://doi.org/10.1080/14735903.2018.1440474

Mdegela RH, Mwakapeje ER, Rubegwa B, Gebeyehu DT, Niyigena S, Msambichaka V, Nonga HE, Antoine-Moussiaux N, Fasina FO. 2021. Antimicrobial use, residues, resistance and governance in the food and agriculture sectors, Tanzania. Antibiotics 10(4), 1–23. https://doi.org/10.3390/antibiotics10040454

Merwan A, Nezif A, Metekia T. 2018. Review on milk and milk product safety, quality assurance and control. International Journal of Livestock Production 9(4), 67–78. https://doi.org/10.5897/ijlp2017.0403

Mizumachi K, Kurisaki JI. 2005. Milk proteins. Nutraceutical Proteins and Peptides in Health and Disease 5(2), 431–444. https://doi.org/10.1016/s0021-9258(18)91668-6

Pan F, Li J, Zhao L, Tuersuntuoheti T, Mehmood A, Zhou N, Hao S, Wang C, Guo Y, Lin W. 2021. A molecular docking and molecular dynamics simulation study on the interaction between cyanidin-3-O-glucoside and major proteins in cow’s milk. Journal of Food Biochemistry 45(1), 1–10. https://doi.org/10.1111/jfbc.13570

Torres PHM, Sodero ACR, Jofily P, Silva-Jr FP. 2019. Key topics in molecular docking for drug design. International Journal of Molecular Sciences 20(18), 1–29. https://doi.org/10.3390/ijms20184574

Trott O, Olson AJ. 2010. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry 31(2), 455–461. https://doi.org/10.1002/jcc.21334

Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, Robinson TP, Teillant A, Laxminarayan R. 2015. Global trends in antimicrobial use in food animals. Proceedings of the National Academy of Sciences of the United States of America 112(18), 5649–5654. https://doi.org/10.1073/pnas.1503141112

Vincent D, Elkins A, Condina MR, Ezernieks V, Rochfort S. 2016. Quantitation and identification of intact major milk proteins for high-throughput LC-ESI-Q-TOF MS analyses. PLoS ONE 11(10), 1–21. https://doi.org/10.1371/journal.pone.0163471

Whitney RM. 1988. Proteins of milk. In Fundamentals of dairy chemistry (pp. 81-169). Boston, MA: Springer US. https://doi.org/10.1007/978-1-4615-7050-9_3

Yao Q, Xing Y, Ma J, Wang C, Zang J, Zhao G. 2021. Binding of Chloroquine to Whey Protein Relieves Its Cytotoxicity while Enhancing Its Uptake by Cells. Journal of Agricultural and Food Chemistry 69(36), 10669–10677. https://doi.org/10.1021/acs.jafc.1c04140

Zhang Y. 2008. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 9, 1–8. https://doi.org/10.1186/1471-2105-9-40

Zhou M, Xia Y, Cao F, Li N, Hemar Y, Tang S, Sun Y. 2019. A theoretical and experimental investigation of the effect of sodium dodecyl sulfate on the structural and conformational properties of bovine β-casein. Soft Matter 15(7), 1551–1561. https://doi.org/10.1039/c8sm01967c