3 Biotech

, 8:373 | Cite as

A molecular simulation analysis of vitamin D targets interleukin 13 (IL13) as an alternative to mometasone in asthma

  • Sriroopreddy Ramireddy
  • P. Raghuraman
  • Pradhyum Khandelwal
  • Jayanthi Abraham
  • C. SudandiradossEmail author
Original Article


Asthma, a chronic lung disease characterized by obstruction of airway passage is characterized by inflammation and hyperresponsiveness with increase in the number of eosinophils. Interleukin-13, plays a significant role in causing inflammation during an asthmatic attack by bronchial constriction. Mometasone, a glucocorticoid has been used as the first line of administration for people affected with asthma for almost a decade. However, in several cases, people treated with mometasone have faced systemic and local side effects. To reduce these side effects, we hypothesized vitamin D that can be used as a substitute to mometasone. For this purpose, we employed the use of molecular docking and simulation studies for comparative study. The docking studies revealed the binding residues of interleukin-13 which are bound to the active site. Among all, we noticed three binding residue Leu83, His84 and Arg86 common for both mometasone and vitamin D. Also, the binding energies share a significant similarity between them. The docked complexes of mometasone and vitamin D with interleukin-13 were evaluated with molecular dynamics simulation. Consistently, the MD analysis uncovered the interesting note on conformational adaptation between the complexes as well as that vitamin D has the complementary binding efficiency to interleukin-13 as compared to mometasone. The substitution of vitamin D might provide a promising gateway to reduce the side effects caused by mometasone and also reduce the cost for treatment of asthma patients.


Asthma Vitamin D Mometasone IL13 Docking Molecular dynamics 



The authors gratefully acknowledge VIT University, Vellore for the support through Seed Grant for this research work.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this paper.


  1. Bendl J, Stourac J, Sebestova E, Vavra O, Musil M, Brezovsky J, Damborsky J (2016) HotSpot Wizard 2.0: automated design of site-specific mutations and smart libraries in protein engineering. Nucleic Acids Res 44:W479–W487. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cave A, Arlett P, Lee E (1999) Inhaled and nasal corticosteroids: factors affecting the risks of systemic adverse effects. Pharmacol Ther 83:153–179CrossRefPubMedGoogle Scholar
  4. Dahl R (2006) Systemic side effects of inhaled corticosteroids in patients with asthma. Respir Med 100:1307–1317. CrossRefPubMedGoogle Scholar
  5. Elias JA, Lee CG, Zheng T, Shim Y, Zhu Z (2003) Interleukin-13 and leukotrienes: an intersection of pathogenetic schema. Am J Respir Cell Mol Biol 28:401–404. CrossRefPubMedGoogle Scholar
  6. Gale CR, Robinson SM, Harvey NC, Javaid MK, Jiang B, Martyn CN, Godfrey KM, Cooper C (2008) Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr 62:68–77. CrossRefPubMedGoogle Scholar
  7. Hanania NA, Chapman KR, Kesten S (1995) Adverse effects of inhaled corticosteroids. Am J Med 98:196–208. CrossRefPubMedGoogle Scholar
  8. Jeffrey GA, Takagi S (1978) Hydrogen-bond structure in carbohydrate crystals. Acc Chem Res 11:264–270. CrossRefGoogle Scholar
  9. Kahn K, Bruice TC (2002) Parameterization of OPLS-AA force field for the conformational analysis of macrocyclic polyketides. J Comput Chem 23:977–996. CrossRefPubMedGoogle Scholar
  10. Kelly HW, Nelson HS (2003) Potential adverse effects of the inhaled corticosteroids. J Allergy Clin Immunol 112:469–478 (quiz 479) CrossRefPubMedGoogle Scholar
  11. Majak P, Olszowiec-Chlebna M, Smejda K, Stelmach I (2011) Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol 127:1294–1296. CrossRefPubMedGoogle Scholar
  12. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785–2791. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Raghuraman P, Jesu Jaya Sudan R, Lesitha Jeeva Kumari J, Sudandiradoss C (2016) Casting the critical regions in nucleotide binding oligomerization domain 2 protein: a signature mediated structural dynamics approach. J Biomol Struct Dyn. CrossRefPubMedGoogle Scholar
  14. Raghuraman P, Jesu Jaya Sudan R, Lesitha Jeeva Kumari J, Sudandiradoss C (2017) Systematic prioritization of functional hotspot in RIG-1 domains using pattern based conventional molecular dynamic simulation. Life Sci 184:58–70. CrossRefPubMedGoogle Scholar
  15. Schüttelkopf AW, van Aalten DMF (2004) PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D Biol Crystallogr 60:1355–1363. CrossRefPubMedGoogle Scholar
  16. Shahin MYA, El-lawah AA, Amin A, El-Tawil IAH (2017) Study of serum vitamin D level in adult patients with bronchial asthma. Egypt J Chest Dis Tuberc 66:5–9. CrossRefGoogle Scholar
  17. Suissa S, Ernst P, Benayoun S, Baltzan M, Cai B (2000) Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 343:332–336. CrossRefPubMedGoogle Scholar
  18. Tachimoto H, Mezawa H, Segawa T, Akiyama N, Ida H, Urashima M (2016) Improved control of childhood asthma with low-dose, short-term Vitamin D supplementation: A randomized, double-blind, placebo-controlled trial. Allergy Eur J Allergy Clin Immunol 71:1001–1009. CrossRefGoogle Scholar
  19. The Universal Protein Resource (UniProt) (2008) Nucleic Acids Res 36:D190–D195. CrossRefGoogle Scholar
  20. Ultsch M, Bevers J, Nakamura G, Vandlen R, Kelley RF, Wu LC, Eigenbrot C (2013) Structural basis of signaling blockade by anti-IL-13 antibody Lebrikizumab. J Mol Biol 425:1330–1339. CrossRefPubMedGoogle Scholar
  21. Wills-Karp M (2004) Interleukin-13 in asthma pathogenesis. Immunol Rev 202:175–190. CrossRefPubMedGoogle Scholar
  22. Wynn TA (2003) IL-13 effector functions. Annu Rev Immunol 21:425–456. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sriroopreddy Ramireddy
    • 1
  • P. Raghuraman
    • 1
  • Pradhyum Khandelwal
    • 1
  • Jayanthi Abraham
    • 2
  • C. Sudandiradoss
    • 1
    Email author
  1. 1.Department of Biotechnology, School of Biosciences and TechnologyVellore Institute of TechnologyVelloreIndia
  2. 2.Microbial Biotechnology Laboratory, School of Biosciences and TechnologyVellore Institute of TechnologyVelloreIndia

Personalised recommendations