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Structural analysis and prediction of potent bioactive molecule for eNOS protein through molecular docking

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Abstract

Reactive oxygen species by uncoupled eNOS is linked to endothelial dysfunction. Ellagic acid (EA), a polyphenol possesses numerous biological activities including radical scavenging. whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels remains unknown. Molecular docking provides an initial model of protein and molecular interactions in various physiological and/or pathological functions. To identify a eNOS modulatory biomolecule through molecular docking as possible vascular protective agent. On the basis of binding affinities and other physicochemical features, a molecular docking-based approach was used to classify and evaluate eNOS binding micronutrients found in natural sources, Lipinski's rule was used taking into account their adsorption, delivery, metabolism, and excretion (ADME). An insilico approach focused on the ligand–protein interaction technique to determine the therapeutic potential of certain phytochemical-based drugs for the vascular remodelling.20 bioactive molecules were screened, docking analysis on human eNOS proteins was performed. The best poses for target protein was established based on binding energy and inhibition constant. EA and caffeine acid are the strongest candidates for eNOS protein functional norms. This provides a novel insight into the interaction properties of known human eNOS protein with EA and used as a therapeutic agent in various pathologies.

Graphic abstract

Predicting interaction of ellagic acid with eNOS protein by molecular docking in endothelial dysfunction.

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References

  • Attique SA, Hassan M, Usman M, Atif RM, Mahboob S, Al-Ghanim KA, Bilal M, Nawaz MZ (2019) A molecular docking approach to evaluate the pharmacological properties of natural and synthetic treatment candidates for use against hypertension. Inter J of envin res and pub heal 16:923

    Article  CAS  Google Scholar 

  • Blom N, Gammeltoft S, Brunak S. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites (1999). Jmol bio;294(5):1351–62.https://doi.org/10.1006/jmbi.1999.3310

  • Boratyn GM, Camacho C, Cooper PS, Coulouris G, Fong A, Ma N, Madden TL, Matten WT, McGinnis SD, Merezhuk Y, Raytselis Y (2013) BLAST: a more efficient report with usability improvements. Nucleic acids research. 41(W1):W29-33. https://doi.org/10.1093/nar/gkt282

    Article  PubMed  PubMed Central  Google Scholar 

  • Devika NT, Amresh P, Hassan MI, Ali BM (2014) Molecular modeling and simulation of the human eNOS reductase domain, an enzyme involved in the release of vascular nitric oxide. J Mol Model. 20:2470. https://doi.org/10.1007/s00894-014-2470-7

    Article  CAS  PubMed  Google Scholar 

  • Fleming I, Busse R (1999) Signal transduction of eNOS activation. Cardiovasc Res 43:532–541. https://doi.org/10.1016/S0008-6363(99)00094-2

    Article  CAS  PubMed  Google Scholar 

  • Förstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J. 33:829–837. https://doi.org/10.3389/fneur.2018.00258

    Article  PubMed  Google Scholar 

  • Forte M, Conti V, Damato A, Ambrosio M, Puca AA, Sciarretta S, Carrizzo A (2016) Targeting nitric oxide with natural derived compounds as a therapeutic strategy in vascular diseases. Oxid Med Cell Longev. https://doi.org/10.1155/2016/7364138

    Article  PubMed  PubMed Central  Google Scholar 

  • Gasteiger E, Hoogland C, Gattiker A, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. In: Walker JM (eds) The proteomics protocols handbook. Springer Protocols Handbooks. Humana Press 571–607. https://doi.org/10.1385/1-59259-890-0:571

  • Gliemann L, Rytter N, Lindskrog M, Slingsby M, Åkerström T, Sylow L, Richter EA, Hellsten Y (2017) Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects. J Physiol 595(16):5557–5571. https://doi.org/10.1113/JP274623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanthe PS, Patil BS, Das KK (2021) Terminalia arjuna supplementation ameliorates high fat diet-induced oxidative stress in nephrotoxic rats. J Basic Clin Physiol Pharmacol

  • Kawashima S, Yokoyama M (2009) Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol 6:998–1005. https://doi.org/10.1161/01.ATV.0000125114.88079.96

    Article  CAS  Google Scholar 

  • Kuo MY, Ou HC, Lee WJ, Kuo WW, Hwang LL, Song TY, Huang CY, Chiu TH, Tsai KL, Tsai CS, Sheu WH (2011a) Ellagic acid inhibits oxidized low-density lipoprotein (OxLDL)-induced metalloproteinase (MMP) expression by modulating the protein kinase C-α/extracellular signal-regulated kinase/peroxisome proliferator-activated receptor γ/nuclear factor-κB (PKC-α/ERK/PPAR-γ/NF-κB) signaling pathway in endothelial cells. J Agri and Food Chem 59(9):5100–5108. https://doi.org/10.1021/jf1041867

    Article  CAS  Google Scholar 

  • Kuo MY, Ou HC, Lee WJ, Kuo WW, Hwang LL, Song TY, Huang CY, Chiu TH, Tsai KL, Tsai CS, Sheu WH (2011b) Ellagic acid inhibits oxidized low-density lipoprotein (OxLDL)-induced metalloproteinase (MMP) expression by modulating the protein kinase C-α/extracellular signal-regulated kinase/peroxisome proliferator-activated receptor γ/nuclear factor-κB (PKC-α/ERK/PPAR-γ/NF-κB) signaling pathway in endothelial cells. J Agric Food Chem 59(9):5100–5108. https://doi.org/10.1021/jf1041867

    Article  CAS  PubMed  Google Scholar 

  • Lima RM, Oliveira LN, Silva MG et al (2019) In silico modulation of the interaction between VEGF and eNOS proteins in atherosclerosis as a future diagnostic and therapeutic approach. J Cardiol Catheter 2019:29–36

    Google Scholar 

  • Majid S, Khanduja KL, Gandhi RK, Kapur S, Sharma RR (1991) Influence of ellagic acid on antioxidant defense system and lipid peroxidation in mice. Biochem Pharmacol. 42(7):1441–5. https://doi.org/10.1016/0006-2952(91)90457-G

    Article  CAS  PubMed  Google Scholar 

  • Marella S, Hema K, Shameer S, Prasad TNVKV (2020) Nano-ellagic acid: inhibitory actions on aldose reductase and α-glucosidase in secondary complications of diabetes, strengthened by in silico docking studies. 3 Biotech 10(10):1–15

    Article  Google Scholar 

  • Mazumder MK, Choudhury S, Borah A (2019) An in silico investigation on the inhibitory potential of the constituents of Pomegranate juice on antioxidant defense mechanism: Relevance to neurodegenerative diseases. IBRO Rep 6:153–159. https://doi.org/10.1016/j.ibror.2019.05.003

    Article  PubMed  PubMed Central  Google Scholar 

  • McWilliam H, Li W, Uludag M, Squizzato S, Park YM, Buso N, Cowley AP, Lopez R (2013) Analysis tool web services from the EMBL-EBI. Nucleic acids Res 41(1):597–600. https://doi.org/10.1093/nar/gkt376

    Article  Google Scholar 

  • Meza CA, La Favor JD, Kim DH, Hickner RC (2019) Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS? Int J Mol Sci 20(15):3775. https://doi.org/10.3390/ijms20153775

    Article  CAS  PubMed Central  Google Scholar 

  • Nikfarjam Z, Bavi O, Amini SK (2021) Potential effective inhibitory compounds against Prostate Specific Membrane Antigen (PSMA): A molecular docking and molecular dynamics study. Arch Biochem Biophys 699:108747

    Article  CAS  Google Scholar 

  • Ou HC, Lee WJ, Lee SD et al (2010) Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway. Toxico App Pharmaco 248(2):134–143. https://doi.org/10.1016/j.taap.2010.07.025

    Article  CAS  Google Scholar 

  • Park SH, Shim BS, Yoon JS, Lee HH, Lee HW, Yoo SB, Oak MH (2015) Vascular protective effect of an ethanol extract of Camellia japonica fruit: endothelium-dependent relaxation of coronary artery and reduction of smooth muscle cell migration. Oxid Med Cell Longev 2016

  • Parvatikar PP, Madagi SB (2018) Molecular docking analysis: interaction studies of natural compounds with human TG2 protein. In the World congress on engineering and computer science.101–11. Springer, Singapore.https://doi.org/10.1007/978-981-15-6848-0_9

  • Petersen TN, Brunak S, Von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nature Methods. 8(10):785–6. https://doi.org/10.1038/nmeth.1701

    Article  CAS  PubMed  Google Scholar 

  • Pinto-Junior VR, Osterne VJS, Santiago MQ, Lossio CF, Nagano CS, Rocha CRC, Nascimento JCF, Nascimento FLF, Silva IB, Oliveira AS, Correia JLA, Leal RB, Assreuy AMS, Cavada BS, Nascimento KS (2017) Molecular modeling, docking and dynamics simulations of the Dioclealasiophylla Mart. Ex Benth seed lectin: An edematogenic and hypernociceptive protein. Biochimie 135:126–136. https://doi.org/10.1016/j.biochi.2017.02.002

    Article  CAS  PubMed  Google Scholar 

  • Rafikov R, Fonseca FV, Kumar S, Pardo D, Darragh C, Elms S, Fulton D, Black SM (2011) eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity. J Endocrinol. 210:271–84. https://doi.org/10.1530/JOE-11-0083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stromsnes K, Mas-Bargues C, Gambini J, Gimeno-Mallench L (2020) Protective effects of polyphenols present in mediterranean diet on endothelial dysfunction. Oxid Med Cell Longev 2097096:1–10. https://doi.org/10.1155/2020/2097096

  • Ulrich Förstermann U, Münzel T (2006) Endothelial nitric oxide synthase in vascular disease from marvel to menace. Circulation 113(13):1708–1714. https://doi.org/10.1161/CIRCULATIONAHA.105.602532

    Article  CAS  PubMed  Google Scholar 

  • Xia N, Horke S, Habermeier A, Closs EI, Reifenberg G, Gericke A, Mikhed Y, Münzel T, Daiber A, Förstermann U, Li H (2016) Uncoupling of endothelial nitric oxide synthase in perivascular adipose tissue of diet-induced obese mice. Arterioscler Thromb Vasc Biol. 36(1):78–85. https://doi.org/10.1161/ATVBAHA.115.306263

    Article  CAS  PubMed  Google Scholar 

  • Yu CS, Lin CJ, Hwang JK (2004) Predicting subcellular localization of proteins for Gram-negative bacteria by support vector machines based on n-peptide compositions. Protein Sci 13(5):1402–6. https://doi.org/10.1110/ps.03479604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Authors are thankful to Shri B.M. Patil Medical College Hospital and Research center, BLDE (DU), Vijayapura for providing fund to carry out present study.

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Authors and Affiliations

  1. Laboratory of Vascular Physiology and Medicine, Department of Physiology, Shri B.M. Patil Medical College Hospital and Research Center, BLDE(DU), Vijayapura, Karnataka, India

    Pallavi S. Kanthe, Kusal K. Das & Prachi P. Parvatikar

  2. Department of Anatomy, Shri B.M. Patil Medical College Hospital and Research Center, BLDE(DU), Vijayapura, Karnataka, India

    Bheemshetty S. Patil

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  1. Pallavi S. Kanthe
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  2. Bheemshetty S. Patil
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Correspondence to Prachi P. Parvatikar.

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Kanthe, P.S., Patil, B.S., Das, K.K. et al. Structural analysis and prediction of potent bioactive molecule for eNOS protein through molecular docking. In Silico Pharmacol. 9, 48 (2021). https://doi.org/10.1007/s40203-021-00106-w

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