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Molecular dynamics investigations for the prediction of molecular interaction of cauliflower mosaic virus transmission helper component protein complex with Myzus persicae stylet’s cuticular protein and its docking studies with annosquamosin-A encapsulated in nano-porous Silica

  • D. Jeya Sundara SharmilaEmail author
  • J. Jino Blessy
  • V. Stephen Rapheal
  • K. S. Subramanian
Original Article


Large numbers of bioactive natural products from plant species such as alkaloids, phenolics, terpenoids etc. are remaining unexplored for their potential as plant protective agents as inhibitors for viral and other pathogenic infections of plant. Myzus aphids are important plant pests and vectors for several plant viruses. Cauliflower mosaic virus (CaMV) belongs to the plant virus family Caulimoviridae which is transmitted “non-circulative” from plant to plant through an interaction with aphid insect vectors. This viral transmission process most likely involves a protein–protein binding interaction between aphid stylet receptor cuticular protein and viral proteins namely, CaMV aphid transmission Helper Component protein and virion associated protein. Aphid stylets are made of cuticle and little is known about the structure of cuticle protein of this insect group. The present study reports the molecular modeling of the structures of Myzus persicae aphid stylet’s cuticular protein (MpsCP) and cauliflower mosaic virus aphid transmission Helper component protein (CaMV HCP). Protein–protein docking studies and molecular dynamics simulations are performed to establish the mode of binding of MpsCP with CaMV HCP. Molecular docking and molecular dynamics investigations of terpenoids Annosquamosin-A from Annona squamosa complex with CaMV transmitting aphid M. persicae stylet’s cuticular protein revealed their means of interaction perhaps relates to restrain viral binding and transmission. QM/MM optimization of mesoporous silica nanopores composite with Annosquamosin-A for smart and safe delivery of bioactive is carried out to study their electronic parameters such as heat of formation, total energy, electronic energy, Ionization potential, Highest Occupied Molecular Orbital, Lowest Un-occupied Molecular Orbital and energy gaps.


Molecular modeling Molecular dynamics Myzus persicae stylet’s cuticle protein Cauliflower mosaic virus aphid transmission Annosquamosin-A Nano-porous silica 



Tamil Nadu Agricultural University is acknowledged for the sanctioned URP No. (NRM/CBE/NST/2015/003) and the authors acknowledge the computational facility by Science and Engineering Research Board, DST (SERB) Ref No. (SR/FT/LS-157/2009), Government of India, New Delhi.

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Alves RH, Reis TVS, Rovani S, Fungaro DA. Green synthesis and characterization of biosilica produced from sugarcane waste ash. J Chem. 2017. Scholar
  2. 2.
    Arkin MR, Tang Y, Wells JA. Small-molecule inhibitors of protein–protein interactions: progressing toward the reality. Chem Biol. 2014;21(9):1102–14.CrossRefGoogle Scholar
  3. 3.
    Bak A, Gargani D, Macia JL, Malouvet E, Vernerey MS, Blanc S, et al. Virus factories of Cauliflower mosaic virus are virion reservoirs that engage actively in vector transmission. J Virol. 2013;87:12207–15.CrossRefGoogle Scholar
  4. 4.
    Blessy JJ, Sharmila DJS. Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin—a molecular dynamics study. Glycoconj J. 2015;32:49–67.CrossRefGoogle Scholar
  5. 5.
    Bowers KJ, Chow E, Xu H, Dror RO, Eastwood MP, Gregersen BA, Klepeis JL, Kolossvary I, Moraes MA, Sacerdoti FD, Salmon JK, Shan Y, Shaw DE. Scalable algorithms for molecular dynamics simulations on commodity clusters. In: SC 2006 conference, proceedings of the ACM/IEEE; 2006. p. 43–3.Google Scholar
  6. 6.
    Chen J, Yan XH, Dong JH, Sang P, Fang X, et al. Tobacco mosaic virus (TMV) inhibitors from Picrasma quassioides benn. J Agric Food Chem. 2009;57:6590–5.CrossRefGoogle Scholar
  7. 7.
    Dáder B, Then C, Berthelot E, Ducousso M, Ng JCK, Drucker M. Insect transmission of plant viruses: multilayered interactions optimize viral propagation. Insect Sci. 2017;24(6):929–46. Scholar
  8. 8.
    Dambolena JS, Zunino MP, Herrera JH, Pizzolitto RP, Areco VA, Zygadlo JA. Terpenes: natural products for controlling insects of importance to human health—a structure-activity relationship study. Psyche A J Entomol. 2016. Scholar
  9. 9.
    Dombrovsky A, Gollop N, Chen S, Chejanovsky N, Raccah B. In vitro association between the helper component-proteinase of zucchini yellow mosaic virus and cuticle proteins of Myzus persicae. J Gen Virol. 2007;88:1602–10.CrossRefGoogle Scholar
  10. 10.
    Dombrovsky A, Huet H, Zhang H, Chejanovsky N, Raccah B. Comparison of newly isolated cuticular protein genes from six aphid species. Insect Biochem Mol Biol. 2003;33:709–15.CrossRefGoogle Scholar
  11. 11.
    Elsharkawy MM, Mousa KM. Induction of systemic resistance against Papaya ring spot virus (PRSV) and its vector Myzus persicae by Penicillium simplicissimum GP17-2 and silica (SiO2) nanopowder. Int J Pest Manag. 2015;61(4):353–8.CrossRefGoogle Scholar
  12. 12.
    Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG. A smooth particle mesh Ewald method. J Chem Phys. 1995;103:8577.CrossRefGoogle Scholar
  13. 13.
    Ferrari S, Pellati F, Costi MP. Protein–protein interaction inhibitors: case studies on small molecules and natural compounds. In: Mangani S, editor. Disruption of protein–protein interfaces. Berlin: Springer; 2013. p. 31–60. Scholar
  14. 14.
    Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK, Shaw DE, Francis P, Shenkin PS. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47:1739–49.CrossRefGoogle Scholar
  15. 15.
    Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein–ligand complexes. J Med Chem. 2006;49:6177–96.CrossRefGoogle Scholar
  16. 16.
    Ge YH, Liu KX, Zhang JX, Mu SZ, Hao XJ. The limonoids and their antitobacco mosaic virus (TMV) activities from Munronia unifoliolata Oliv. J Agric Food Chem. 2012;60:4289–95.CrossRefGoogle Scholar
  17. 17.
    Hebrard E, Drucker M, Leclerc D, Hohn T, Uzest M, Froissart R, Strub JM, Sanglier S, van Dorsselaer A, Padilla A, Labesse G, Blanc S. Biochemical characterization of the helper component of Cauliflower mosaic virus. J Virol. 2001;75(18):8538–46.CrossRefGoogle Scholar
  18. 18.
    Hoh F, Uzest M, Drucker M, Plisson-Chastang C, Bron P, Blanc S, Dumas C. Structural insights into the molecular mechanisms of Cauliflower mosaic virus transmission by its insect vector. J Virol. 2010;84(9):4706–13. Scholar
  19. 19.
    Iconomidou VA, Willis JH, Hamodrakas SJ. Unique features of the structural model of ‘hard’ cuticle proteins: implications for chitin-protein interactions and cross-linking incuticle. Insect Biochem Mol Biol. 2005;35(6):553–60.CrossRefGoogle Scholar
  20. 20.
    Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79:926.CrossRefGoogle Scholar
  21. 21.
    Lembo D, Cavalli R. Nanoparticulate delivery systems for antiviral drugs. Antivir Chem Chemother. 2010;21(2):53–70. Scholar
  22. 22.
    Lengauer T, Rarey M. Computational methods for biomolecular docking. Curr Opin Struct Biol. 1996;6:402–6.CrossRefGoogle Scholar
  23. 23.
    Liang Y, Gao XW. The cuticle protein gene MPCP4 of Myzus persicae (Homoptera: Aphididae) plays a critical role in cucumber mosaic virus acquisition. J Econ Entomol. 2017;110(3):848–53. Scholar
  24. 24.
    Lin CY, Wu DC, Yu JZ, Chen BH, Wang CL, Ko WH. Control of silverleaf whitefly, cotton aphid and kanzawa spider mite with oil and extracts from seeds of sugar apple. Neotrop Entomol. 2009;38(4):531–6.CrossRefGoogle Scholar
  25. 25.
    Mann RS, Kaufman PE. Natural product pesticides: their development, delivery and use against insect vectors. Mini-Rev Org Chem. 2012;9(2):185–202. Scholar
  26. 26.
    Moreno A, Hebrard E, Uzest M, Blanc S, Fereres A. A single amino acid position in the helper component of Cauliflower mosaic virus can change the spectrum of transmitting vector species. J Virol. 2005;79:13587–93.CrossRefGoogle Scholar
  27. 27.
    Mullard A. Protein–protein interaction inhibitors get into the groove. Nat Rev Drug Discov. 2012;11(3):173–5. Scholar
  28. 28.
    Nuruzzaman M, Rahman MM, Liu Y, Naidu R. Nanoencapsulation, nano-guard for pesticides: a new window for safe application. J Agric Food Chem. 2016;64:1447–83.CrossRefGoogle Scholar
  29. 29.
    Rahman NA, Widhiana I, Juliastuti SR, Setyawan H. Synthesis of mesoporous silica with controlled pore structure from bagasse ash as a silica source. Colloids Surf A Physicochem Eng Asp. 2015;476:1–7.CrossRefGoogle Scholar
  30. 30.
    Roy A, Kucukural A, Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc. 2010;5:725–38.CrossRefGoogle Scholar
  31. 31.
    Ryckaert JP, Ciccotti G, Berendsen HJC. Numerical integration of cartesian equations of motion of a system with constraints: molecular dynamics of N-alkanes. J Comput Phys. 1977;23:327–41.CrossRefGoogle Scholar
  32. 32.
    Sakr N. Silicon control of bacterial and viral diseases in plants. J Plant Prot Res. 2016;56(4):331–6.CrossRefGoogle Scholar
  33. 33.
    Shan Y, Kim ET, Eastwood MP, Dror RO, Seeliger MA, Shaw DE. How does a drug molecule find its target binding site? J Am Chem Soc. 2011;133:9181–3.CrossRefGoogle Scholar
  34. 34.
    Shanks CH, Chapman RK. The use of antiviral chemicals to protect plants against some viruses transmitted by aphids. Virology. 1965;25:f13–7.CrossRefGoogle Scholar
  35. 35.
    Sharmila DJS, Blessy JJ. Molecular dynamics of sialic acid analogues complex with cholera toxin and DFT optimization of ethylene glycol-mediated zinc nanocluster conjugation. J Biomol Struct Dyn. 2017;35(1):182–206.CrossRefGoogle Scholar
  36. 36.
    Shelley JC, Cholleti A, Frye LL, Greenwood JR, Timlin MR, Uchimaya M. Epik: a software program for pK a prediction and protonation state generation for drug-like molecules. J Comput Aided Mol Des. 2007;21:681–91.CrossRefGoogle Scholar
  37. 37.
    Sheng C, Dong G, Miao Z, Zhang W, Wang W. State-of-the-art strategies for targeting protein–protein interactions by small-molecule inhibitors. Chem Soc Rev. 2015;44(22):8375. Scholar
  38. 38.
    Stewart JJP. Stewart Computational Chemistry, Colorado Springs, CO, USA, MOPAC 2016; 2016.
  39. 39.
    Strahan GD, Keniry MA, Shafer RH. NMR structure refinement and dynamics of the K+-[d(G3T4G3)]2 quadruplex via particle mesh Ewald molecular dynamics simulations. Biophys J. 1998;75:968–81.CrossRefGoogle Scholar
  40. 40.
    Sun HD, Huang SX, Han QB. Diterpenoids from Isodon species and their biological activities. Nat Prod Rep. 2006;23(5):673–98.CrossRefGoogle Scholar
  41. 41.
    Syller J. The roles and mechanisms of helper component proteins encoded by potyviruses and caulimoviruses. Physiol Mol Plant Pathol. 2006;67:119–30.CrossRefGoogle Scholar
  42. 42.
    Whitfield AE, Falk BW, Rotenberg D. Insect vector-mediated transmission of plant viruses. Virology. 2015;479–480:278–89.CrossRefGoogle Scholar
  43. 43.
    Wu YC, Hung YC, Chang FR, Cosentino M, Wang HK, Lee KH. Identification of ent-16 beta, 17-dihydroxykauran-19-oic acid as an anti-HIV principle and isolation of the new diterpenoids annosquamosins A and B from Annona squamosa. J Nat Prod. 1996;59(6):635–7.CrossRefGoogle Scholar
  44. 44.
    Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y. The I-TASSER suite: protein structure and function prediction. Nat Methods. 2015;12:7–8.CrossRefGoogle Scholar
  45. 45.
    Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinform. 2008;9:40.CrossRefGoogle Scholar
  46. 46.
    Zhao P, Cao L, Ma D, Zhou Z, Huang Q, Pan C. Synthesis of pyrimethanil-loaded mesoporous silica nanoparticles and its distribution and dissipation in cucumber plants. Molecules. 2017;22(5):817–29. Scholar

Copyright information

© Indian Virological Society 2019

Authors and Affiliations

  1. 1.Department of Nano Science and TechnologyTamil Nadu Agricultural UniversityCoimbatoreIndia
  2. 2.Department of BiotechnologyKumaraguru College of TechnologyCoimbatoreIndia

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