Skip to main content
SpringerLink
Log in

Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural behavior, electrostatic and energetic analysis

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

The dynamic behavior of the HCV IRES IIId domain is analyzed by means of a 2.6-ns molecular dynamics simulation, starting from an NMR structure. The simulation is carried out in explicit water with Na+ counterions, and particle-mesh Ewald summation is used for the electrostatic interactions. In this work, we analyze selected patterns of the helix that are crucial for IRES activity and that could be considered as targets for the intervention of inhibitors, such as the hexanucleotide terminal loop (more particularly its three consecutive guanines) and the loop-E motif. The simulation has allowed us to analyze the dynamics of the loop substructure and has revealed a behavior among the guanine bases that might explain the different role of the third guanine of the GGG triplet upon molecular recognition. The accessibility of the loop-E motif and the loop major and minor groove is also examined, as well as the effect of Na+ or Mg2+ counterion within the simulation. The electrostatic analysis reveals several ion pockets, not discussed in the experimental structure. The positions of these ions are useful for locating specific electrostatic recognition sites for potential inhibitor binding.

Figure Superposition of 14 structures representative of the evolution of IRES IIId RNA along 2.6-ns MD simulation

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1 a
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Tsukiyama-Kohara K, Iizuka N, Kohara M, Nomoto A (1992) J Virol 66:1476–1483

    CAS  PubMed  Google Scholar 

  2. Fukushi S, Katayama K, Kurihara C, Ishiyama N, Hoshino FB, Ando T, Oya A (1994) Biochem Biophys Res Commun 199:425–432

    Article  CAS  PubMed  Google Scholar 

  3. Honda M, Brown EA, Lemon SM (1996) RNA 2:955–968

    CAS  PubMed  Google Scholar 

  4. Jubin R, Vantuno NE, Kieft JS, Murray MG, Doudna JA, Lau JYN, Baroudy BM (2000) J Virol 74:10430–10437

    Article  CAS  PubMed  Google Scholar 

  5. Kolupaeva VG, Pestova TV, Hellen CU (2000) J Virol 74:6442–6450

    Article  PubMed  Google Scholar 

  6. Kieft JS, Zhou K, Jubin R, Murray MG, Lau JYN, Doudna JA (1999) J Mol Biol 292:513–529

    Article  CAS  PubMed  Google Scholar 

  7. Lukavsky PJ, Otto GA, Lancaster M, Sarnow P, Puglisi JD (2000) Nature Struct Bio 7:1105–1110

    Article  CAS  Google Scholar 

  8. Klinck R, Westhof E, Walker S, Afshar M, Collier A, Aboul-Ela F (2000) RNA 6:1423–1431

    Article  CAS  PubMed  Google Scholar 

  9. Case DA, Pearlman DA, Caldwell JW, Cheatham TEI, Ross WS, Simmerling C, Darden T, Merz KMJ, Stanton RV, Chen A, Vincent JJ, Crowley M, Tsui V, Radmer R, Duan Y, Pitera J, Massova I, Seibel GL, Singh UC, Weiner P, Kollman PA (2000) AMBER 6. University of California, San Francisco, Calif.

  10. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) J Chem Phys 79:926–935

    CAS  Google Scholar 

  11. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, ZakrzewskiVG, Montgomery JA, Stratmann RE, Burant JC, Dapprich S, Millam JM, Daniles AD, Kudin KN, Strain MC, Farkas O, Tomasi J, Barone V, Cossi M, Cammi R, Mennucci B, Pomelli C, Adamo C, Clifford S, Ochterski J, Petersson GA, Ayala PY, Cui Q, Morokuma K, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Cioslowski J, Ortiz JV, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Gomperts R, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Gonzalez C, Challacombe M, Gill PMW, Johnson BG, Chen W, Wong MW, Andres JL, Head-Gordon M, Replogle ES, Pople JA (1998) Gaussian 98. Gaussian, Pittsburg, Pa.

  12. Kollman PA, Dixon R, Cornell W, Fox T, Chipot C, Pohorille A (1997) In: Wilkinson PWA, van Gunsteren W (ed) Computer simulation of biomolecular systems: theoretical and experimental applications, vol 3. Escom, The Netherlands, p 83

  13. Hobza P, Kabelàc M, Šponer J, Mejzlik P, Vondrasek J (1997) J Comput Chem 97:1136–1150

    Article  Google Scholar 

  14. Hobza P, Šponer J (1999) Chem Rev 99:3247–3276

    Article  CAS  PubMed  Google Scholar 

  15. Auffinger P, Westhof E (2000) J Mol Biol 300:1115–1133

    Article  Google Scholar 

  16. Auffinger P, Westhof E (2001) Biopolymers 56:266–274

    Article  Google Scholar 

  17. Auffinger P, Westhof E (2001) J Mol Biol 305:1057–1072

    Article  CAS  PubMed  Google Scholar 

  18. Auffinger P, Westhof E (1997) J Mol Biol 269:326–341

    CAS  PubMed  Google Scholar 

  19. Schneider C, Brandl M, Sühnel J (2001) J Mol Biol 305:659–667

    Article  CAS  PubMed  Google Scholar 

  20. Yang X, Gerczei T, Glover L, Correll CC (2001) Nat Struct Biol 8:968–973

    Article  CAS  PubMed  Google Scholar 

  21. Leontis NB, Westhof E (1998) J Mol Biol 283:571–583

    Article  CAS  PubMed  Google Scholar 

  22. Weeks KM, Crothers DM (1993) Science 261:1574–1577

    CAS  PubMed  Google Scholar 

  23. Gao YG, Robinson H, van Boom JH, Wang AJH (1995) Biophys J 69:559–568

    CAS  PubMed  Google Scholar 

  24. Young MA, Jayaram B, Beveridge DL (1997) J Am Chem Soc 119:59–69

    Article  CAS  Google Scholar 

  25. Serra MJ, Baird JD, Dale T, Fey BL, Retatagos K, Westhof E (2002) RNA 8:307–323

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The CINES computing center is acknowledged for providing us with computing time. JG thanks Adrian Wiley for his help in the preparation of the manuscript and Juan Fernandez Carmona for the energy calculations. The referees are acknowledged for interesting suggestions.

Author information

Authors and Affiliations

  1. Laboratoire Arômes Synthèses Interactions, Faculté des Sciences de Nice Sophia-Antipolis, 06108 cedex 2, Nice, France

    Jérôme Golebiowski, Serge Antonczak & Daniel Cabrol-Bass

  2. Laboratoire de Chimie Bioorganique, Faculté des Sciences de Nice Sophia-Antipolis, 06108 cedex 2, Nice, France

    Audrey Di-Giorgio & Roger Condom

Authors
  1. Jérôme Golebiowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serge Antonczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Audrey Di-Giorgio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roger Condom
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel Cabrol-Bass
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jérôme Golebiowski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Golebiowski, J., Antonczak, S., Di-Giorgio, A. et al. Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural behavior, electrostatic and energetic analysis. J Mol Model 10, 60–68 (2004). https://doi.org/10.1007/s00894-003-0170-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00894-003-0170-9

Keywords

Search

Navigation