Skip to main content
SpringerLink
Log in

Enhancing the accuracy of virtual screening: molecular dynamics with quantum-refined force fields

  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Summary

A methodology aimed at improving the accuracy of current docking–scoring procedures is proposed, and validated through detailed tests of its performance in predicting the activity of HIV-1 protease inhibitors. This methodology is based on molecular dynamics simulations using a force field whose effective charges are refined by means of a novel procedure that relies on quantum-mechanical calculations and preserves the internal consistency of the parameterization scheme.

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.

Similar content being viewed by others

References

  1. P.D. Lyne (2002) ArticleTitleDrug Discov Today 7 1047 Occurrence Handle1:CAS:528:DC%2BD38XnsF2ksr0%3D

    CAS  Google Scholar 

  2. H. Gohlke G. Klebe (2002) ArticleTitleAngew Chem. Int. Ed. Engl. 41 2644 Occurrence Handle10.1002/1521-3773(20020802)41:15<2644::AID-ANIE2644>3.0.CO;2-O Occurrence Handle1:CAS:528:DC%2BD38Xmt1entbw%3D

    Article  CAS  Google Scholar 

  3. B.J. McConkey V. Sobolev M. Edelman (2002) Curr Sci., 83 IssueID845 83 845

    Google Scholar 

  4. R.G. Parr W. Yang (1989) Density Functional Theory of Atoms and Molecules Oxford University Press New York.

    Google Scholar 

  5. CPMD V3.7 Copyright IBM Corp. 1990–2003, Copyright MPI für Festkörperforschung Stuttgart 1997–2001. See http://www.cpmd.org.

  6. F. (a) Momany (1984) ArticleTitleJ. Phys. Chem., 82 (1978) 592; (b) Singh U.C. and Kollman, P.A., J. Comput. Chem 5 129 Occurrence Handle10.1002/jcc.540050204

    Article  Google Scholar 

  7. T. Mordasini A. Curioni R. Bursi W. Andreoni (2003) ChemBioChem 4 155 Occurrence Handle10.1002/cbic.200390026 Occurrence Handle1:CAS:528:DC%2BD3sXitFyksLg%3D Occurrence Handle12616628

    Article  CAS  PubMed  Google Scholar 

  8. Holloway, M.K., Wai, J.M., Halgren, T.A, Fitzgerald, P.M.D., Vacca, J.P., Dorsey, B.D., Levin, R.B., Thompson, W.J., Chen, L.J., deSolms, S.J., Gaffin, N., Ghosh, A.K., Giuliani, E.A., Graham, S.L., Guare, J.P., Hungate, R.W., Lyle, T.A., Sanders, W.M., Tucker, T.J., Wiggins, M., Wiscount, C.M., Woltersdorf, O.W., Young, S.D., Darke, P.L. and Zugay, J.A., J. Med. Chem., 38 (1995) 305.

  9. van Gunsteren, W.F., Billeter, S.R., Eising, A.A., Hünenberger, P.H., Krüger, P., Mark, A.E., Scott, W.R.P. and Tironi, I.G. Biomolecular Simulation: The GROMOS96 Manual and User Guide, vdF: Hochschulverlag AG an der ETH Zürich and BIOMOS B.V., Zürich, Switzerland, Groningen, The Netherlands, 1996, ISBN 3 7281 2422 2.

  10. H.J.C. Berendsen J.P.M. Postma W.F. Gunsteren Particlevan J. Hermans B. Pullman (1981) Intermolecular Forces Reidel, Dordrecht The Netherlands 331–342

    Google Scholar 

  11. N. Troullier J.L. Martins (1991) Phys Rev. B, 43 1993

    Google Scholar 

  12. C.I. Bayly P. Cieplak W.D. Cornell P.A. Kollman (1993) J Phys Chem 97 10269 Occurrence Handle10.1021/j100142a004 Occurrence Handle1:CAS:528:DyaK3sXlvVyqsLs%3D

    Article  CAS  Google Scholar 

  13. A.D. Becke (1988) Phys. Rev. A 38 3098 Occurrence Handle1:CAS:528:DyaL1cXmtlOhsLo%3D Occurrence Handle9900728

    CAS  PubMed  Google Scholar 

  14. C. Lee W. Yang R.G. Parr (1988) Phys. Rev. B, 37 785

    Google Scholar 

  15. D.A. Pearlman D.A. Case J.W. Caldwell W.S. Ross T.E. Cheatham SuffixIII S. DeBolt D. Ferguson G. Seibel P. Kollman (1995) Comp Phys. Commun. 91 1 Occurrence Handle10.1016/0010-4655(95)00041-D Occurrence Handle1:CAS:528:DyaK2MXps1Wrtrw%3D

    Article  CAS  Google Scholar 

  16. P.M.D. Fitzgerald B.M. McKeever J.F. Van Middlesworth J.P. Springer J.C. Heimbach C.-T. Leu W.K. Herber R.A.F. Dixon P.L. Darke (1990) J. Biol. Chem. 265 14209 Occurrence Handle1:CAS:528:DyaK3cXls1Oqsrs%3D Occurrence Handle2201682

    CAS  PubMed  Google Scholar 

  17. J.H. Lin D. Ostovic J.P. Vacca R.T. Borchardt (1998) Integration of Pharmaceutical Discovery and Development: Case Studies Chapter 11 Plenum Press New York 233–255

    Google Scholar 

  18. W.F. Gunsteren Particlevan W.F. Gunsteren Particlevan P.K. Weiner (1989) Computer Simulation of Biomolecular Systems, Theoretical and Experimental Applications Escom Science Publishers Leiden 27–59

    Google Scholar 

  19. T.P. Straatsma J.A. McCammon (1991) J., Chem Phys 95 1175

    Google Scholar 

  20. T.C. Beutler A.E. Mark R.C. Schaik Particlevan P.R. Gerber W.F. Gunsteren Particlevan (1994) Chem Phys. Lett. 222 529 Occurrence Handle10.1016/0009-2614(94)00397-1 Occurrence Handle1:CAS:528:DyaK2cXksVCis7w%3D

    Article  CAS  Google Scholar 

  21. C.N. Hodge T.P. Straatsma J.A. McCammon A. Wlodawer W. Chiu R.M. Burnett R. Garcea (1997) Structural Biology of Viruses Oxford University Press. New York.

    Google Scholar 

  22. R.D. Taylor P.J. Jewsbury J.W. Essex (2002) J. Comput- Aided Mol. Des. 16 151 Occurrence Handle10.1023/A:1020155510718 Occurrence Handle1:CAS:528:DC%2BD38XotFekurg%3D Occurrence Handle12363215

    Article  CAS  PubMed  Google Scholar 

  23. Zhou R., Friesner R.A., Ghosh A., Rizzo R.C., Jorgensen W.L., Levy R.M. (2003). J. Phys. Chem., 105 (2001) 10388; Zoete, V., Michielin O. and Karplus M., J. Comput.-Aided. Mol. Des., 17: 861.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. IBM Research, Zurich Research Laboratory, CH-8803, Rüschlikon, Switzerland

    Alessandro Curioni, Tiziana Mordasini & Wanda Andreoni

Authors
  1. Alessandro Curioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiziana Mordasini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wanda Andreoni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alessandro Curioni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Curioni, A., Mordasini, T. & Andreoni, W. Enhancing the accuracy of virtual screening: molecular dynamics with quantum-refined force fields. J Comput Aided Mol Des 18, 773–784 (2004). https://doi.org/10.1007/s10822-004-7881-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10822-004-7881-6

Keywords

Search

Navigation