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SAMPL2 and continuum modeling

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Abstract

An account is given of our contributions to the SAMPL2 challenge for vacuum-water transfer energies. These contributions include different charge sets and radii used with Poisson–Boltzmann continuum theory applied to a single low-energy conformation. A rationale for this approach is given, including a summary of what we have learnt over previous SAMPL events. The results strongly suggest the need for new and repeated experimental measurements, both to clarify what appears to be experimental discrepancies in older measurements and to advance the field in a statistically sound manner.

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References

  1. Nicholls A, Mobley DL, Guthrie JP, Chodera JD, Bayly CI, Cooper MD, Pande VS (2008) Predicting small-molecule solvation free energies: an informal blind test for computational chemistry. J Med Chem 51(4):769–779

    Article  CAS  Google Scholar 

  2. Skillman AG, Nicholls A (2008) SAMPL2: statistical analysis of the modeling of proteins and ligands

  3. Nicholls A, Wlodek S, Grant JA (2009) The SAMP1 solvation challenge: further lessons regarding the pitfalls of parametrization. J Phys Chem B 113(14):4521–4532

    Article  CAS  Google Scholar 

  4. Jakalian A, Jack DB, Bayly CI (2002) Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation. J Comput Chem 23(16):1623–1641

    Article  CAS  Google Scholar 

  5. Zhao Y, Truhlar DG (2006) A density functional that accounts for medium-range correlation energies in organic chemistry. Org Lett 8(25):5753–5755

    Article  CAS  Google Scholar 

  6. Grant AJ, Pickup BT, Nicholls A (2001) A smooth permittivity function for Poisson–Boltzmann solvation methods. J Comp Chem 22:608–640

    Article  CAS  Google Scholar 

  7. Gilson M, Rashin A, Fine R, Honig B (1985) On the calculation of electrostatic interactions in proteins. J Mol Biol 184:503–516

    Article  CAS  Google Scholar 

  8. Nicholls A, Honig B (1991) A rapid finite difference algorithm, utilizing successive over-relaxation to solve the Poisson–Boltzmann equation. J Comp Chem 12(4):435–445

    Article  CAS  Google Scholar 

  9. OMEGA http://www.eyesopen.com/products/applications/omega.html

  10. SZYBKI http://www.eyesopen.com/products/applications/szybki.html

  11. Hertwig RH, Koch W (1997) On the parameterization of the local correlation functional. What is Becke-3-LYP? Chem Phys Lett 268(5–6):345–351

    Article  CAS  Google Scholar 

  12. Gaussian I. www.gaussian.com

  13. Singh UC, Kollman PA (1994) An approach to computing electrostatic charges for molecules. J Comp Chem 5(2):129–145

    Article  Google Scholar 

  14. QUACPAC http://www.eyesopen.com/products/applications/quacpac.html

  15. Ellingson BA, Skillman AG, Nicholls A (2010) Analysis of SM8 and Zap TK calculations and their geometric sensitivity. JCAMD 24. doi:10.1007/s10822-010-9355-3

  16. Bondi A (1964) J Phys Chem 64:441

    Article  Google Scholar 

  17. Kelly CP, Cramer CJ, Truhlar DG (2005) SM6: a density functional theory continuum solvation model for calculating aqueous solvation free energies of neutrals, ions, and solute-water clusters. J Chem Theory Comput 1:1133–1152

    Article  CAS  Google Scholar 

  18. Sharp KA, Nicholls A, Fine RF, Honig B (1991) Reconciling the magnitude of the microscopic and macroscopic hydrophobic effects. Science 252(5002):106–109

    Article  CAS  Google Scholar 

  19. Jones FM, Arnett EM (1974) Prog Phys Org Chem 11:263–322

    Article  CAS  Google Scholar 

  20. Ben-Naim A, Marcus Y (1984) J Chem Phys 81:2016–2027

    Article  CAS  Google Scholar 

  21. Marten B, Kim K, Cortis C, Friesner RA, Murphy RB, Ringnalda MN, Sitkoff D, Honig B (1996) J Phys Chem 100:11775–11788

    Article  CAS  Google Scholar 

  22. Rizzo RC, Jorgensen WL (1999) OPLS all-atom model for amines: resolution of the amine hydration problem. JACS 121:4827–4836

    Article  CAS  Google Scholar 

  23. McClellan AL (1963) Tables of experimental dipole moments, 1st edn. W. H. Freeman and Co., New York

    Google Scholar 

  24. Mobley DL, Dill KA, Chodera JD (2008) Treating entropy and conformational changes in implicit solvent simulations of small molecules. J Phys Chem B 112(3):938–946

    Article  CAS  Google Scholar 

  25. Rashin AA, Honig B (1985) Reevaluation of the Born model of ion hydration. J Phys Chem 89(26):5588–5593

    Article  CAS  Google Scholar 

  26. Geballe M, Skillman AG, Nicholls A, Guthrie JP, Taylor PJ (2010) The SAMPL2 blind prediction challenge: introduction and overview. JCAMD 24. doi:10.1007/s10822-010-9350-8

  27. Ren P, Ponder JW (2003) Polarizable atomic multipole water model for molecular mechanics simulation. J Phys Chem B 107:5933–5947

    Article  CAS  Google Scholar 

  28. Lide DR (ed) (1998) CRC handbook of chemistry and physics, 79th edn. CRC Press, Boco Raton

  29. Gallicchio E, Zhang LY, Levy RM (2002) The SGB/NP hydration free energy model based on the surface generalized born solvent reaction field and novel nonpolar hydration free energy estimators. J Comput Chem 23(5):517–529

    Article  CAS  Google Scholar 

  30. Sitkoff D, Sharp K, Honig B (1994) Accurate calculation of hydration free energies using macroscopic solvent models. J Phys Chem 98:1978–1988

    Article  CAS  Google Scholar 

  31. Bordner AJ, Cavasotto CN, Abagyan RA (2002) Accurate transferable model for water, n-Octanol and n-Hexadecane solvation free energies. J Phys Chem B 106:11009–11015

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. OpenEye Scientific Software, Inc, Santa Fe, NM, 87508, USA

    Anthony Nicholls & Stanislaw Wlodek

  2. AstraZeneca Pharmaceuticals, Mereside, Macclesfield, SK10 4TF, Cheshire, UK

    J. Andrew Grant

Authors
  1. Anthony Nicholls
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  2. Stanislaw Wlodek
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  3. J. Andrew Grant
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Corresponding author

Correspondence to Stanislaw Wlodek.

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Nicholls, A., Wlodek, S. & Grant, J.A. SAMPL2 and continuum modeling. J Comput Aided Mol Des 24, 293–306 (2010). https://doi.org/10.1007/s10822-010-9334-8

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