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Journal of Computer-Aided Molecular Design

, Volume 26, Issue 1, pp 93–95 | Cite as

Let’s get honest about sampling

  • David L. MobleyEmail author
Perspective

Abstract

Molecular simulations see widespread and increasing use in computation and molecular design, especially within the area of molecular simulations applied to biomolecular binding and interactions, our focus here. However, force field accuracy remains a concern for many practitioners, and it is often not clear what level of accuracy is really needed for payoffs in a discovery setting. Here, I argue that despite limitations of today’s force fields, current simulation tools and force fields now provide the potential for real benefits in a variety of applications. However, these same tools also provide irreproducible results which are often poorly interpreted. Continued progress in the field requires more honesty in assessment and care in evaluation of simulation results, especially with respect to convergence.

Keywords

Sampling Convergence Force fields and molecular simulations Binding affinity 

Notes

Acknowledgements

DLM acknowledges the Louisiana Board of Regents Research Competitiveness and Research Enhancement Subprograms as well as the Louisiana Optical Network Initiative (supported by the Louisiana Board of Regents Post-Katrina Support Fund Initiative grant LEQSF(2007-12)- ENH-PKSFI-PRS-01), and the National Science Foundation under NSF EPSCoR Cooperative Agreement No. EPS-1003897 with additional support from the Louisiana Board of Regents.

References

  1. 1.
    Merz KM Jr (2010) J Chem Theory Comput 6(5):1769CrossRefGoogle Scholar
  2. 2.
    Faver JC, Benson ML, He X, Roberts BP, Wang B, Marshall MS, Kennedy MR, Sherrill CD, Merz KM Jr (2011) J Chem Theory Comput 7(3):790CrossRefGoogle Scholar
  3. 3.
    Deng Y, Roux B (2008) J Chem Phys 128(11):115103CrossRefGoogle Scholar
  4. 4.
    Fujitani H, Tanida Y, Matsuura A (2009) Phys Rev E 79(2):21914CrossRefGoogle Scholar
  5. 5.
    Karney CFF, Ferrara JE, Brunner S (2005) J Comput Chem 26(3):243CrossRefGoogle Scholar
  6. 6.
    Boyce SE, Mobley DL, Rocklin GJ, Graves AP, Dill KA, Shoichet BK (2009) J Mol Biol 394(4):747CrossRefGoogle Scholar
  7. 7.
    Schlick T (2010) Molecular modeling and simulation: an interdisciplinary guide, interdisciplinary applied mathematics, vol 21, 2nd edn. Springer, New YorkGoogle Scholar
  8. 8.
    Mobley DL, Graves AP, Chodera JD, McReynolds A, Shoichet BK, Dill KA (2007) J Mol Biol 371:1118CrossRefGoogle Scholar
  9. 9.
    Jayachandran G, Shirts MR, Park S, Pande VS (2006) J Chem Phys 125(8):084901CrossRefGoogle Scholar
  10. 10.
    Steinbrecher T, Case D, Labahn A (2006) J Med Chem 49(6):1837CrossRefGoogle Scholar
  11. 11.
    Mobley DL, Dill KA (2009) Structure 17(4):489CrossRefGoogle Scholar
  12. 12.
    Mobley DL, Chodera JD, Dill KA (2007) J Chem Theory Comput 3(4):1231CrossRefGoogle Scholar
  13. 13.
    Gallicchio E, Levy RM (2011) Curr Opin Struct Biol 21(2):161CrossRefGoogle Scholar
  14. 14.
    Gallicchio E, Lapelosa M, Levy RM (2010) J Chem Theory Comput 6(9):2961CrossRefGoogle Scholar
  15. 15.
    Luccarelli J, Michel J, Tirado-Rives J, Jorgensen WL (2010) J Chem Theory Comput 6(12):3850CrossRefGoogle Scholar
  16. 16.
    Michel J, Essex JW (2010) J Comput Aided Mol Des 24:638–658CrossRefGoogle Scholar
  17. 17.
    Leitgeb M, Schröder C, Boresch S (2005) J Chem Phys 122(8):084109CrossRefGoogle Scholar
  18. 18.
    Klimovich P, Mobley DL (2010) J Comput Aided Mol Des 24(4):307CrossRefGoogle Scholar
  19. 19.
    Paluch AS, Mobley DL, Maginn EJ (2011) J Chem Theory Comput 7(9):2910CrossRefGoogle Scholar
  20. 20.
    Lindorff-Larsen K, Piana S, Dror RO, Shaw DE (2011) Science 334(6055):517CrossRefGoogle Scholar
  21. 21.
    Dror RO, Pan AC, Arlow DH, Borhani DW, Maragakis P, Shan Y, Xu H, Shaw DE (2011) Proc Natl Acad Sci 108(32):13118CrossRefGoogle Scholar
  22. 22.
    Shan Y, Kim ET, Eastwood MP, Dror RO, Seeliger MA, Shaw DE (2011) J Am Chem Soc 133(24):9181CrossRefGoogle Scholar
  23. 23.
    Mobley DL, Chodera JD, Dill KA (2006) J Chem Phys 125:084902CrossRefGoogle Scholar
  24. 24.
    Dolenc J, Oostenbrink C, Koller J, van Gunsteren W (2005) Nucleic Acids Res 33(2):725CrossRefGoogle Scholar
  25. 25.
    Shirts MR, Mobley D, Brown SP (2010) In: Merz KM, Ringe D, Reynolds CH (eds) Drug design: structure- and ligand-based approaches, Cambridge University PressGoogle Scholar
  26. 26.
    Mobley DL, Dumont É, Chodera JD, Dill K (2007) J Phys Chem B 111(9):2242CrossRefGoogle Scholar
  27. 27.
    Mobley DL, Bayly CI, Cooper MD, Shirts MR, Dill KA (2009) J Chem Theory Comput 5(2):350CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of New OrleansNew OrleansUSA

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