Journal of Computer-Aided Molecular Design

, Volume 24, Issue 4, pp 259–279 | Cite as

The SAMPL2 blind prediction challenge: introduction and overview

  • Matthew T. GeballeEmail author
  • A. Geoffrey Skillman
  • Anthony Nicholls
  • J. Peter Guthrie
  • Peter J. Taylor


The interactions between a molecule and the aqueous environment underpin any process that occurs in solution, from simple chemical reactions to protein–ligand binding to protein aggregation. Fundamental measures of the interaction between molecule and aqueous phase, such as the transfer energy between gas phase and water or the energetic difference between two tautomers of a molecule in solution, remain nontrivial to predict accurately using current computational methods. SAMPL2 represents the third annual blind prediction of transfer energies, and the first time tautomer ratios were included in the challenge. Over 60 sets of predictions were submitted, and each participant also attempted to estimate the error in their predictions, a task that proved difficult for most. The results of this blind assessment of the state of the field for transfer energy and tautomer ratio prediction both indicate where the field is performing well and point out flaws in current methods.


Solvation Transfer energy Tautomers Blind prediction Validation 


  1. 1.
    Hastie T, Tibshirani R, Friedman J (2009) The elements of statistical learning: data mining, inference, and prediction, 2nd edn. Springer, BerlinGoogle Scholar
  2. 2.
    Bordner A, Cavasotto C, Abagyan R, Phys J (2002) Chem. B 106:11009–11015Google Scholar
  3. 3.
    Cramer C, Truhlar D (2008) Acc Chem Res 41:760–768CrossRefGoogle Scholar
  4. 4.
    Klamt A, Mennucci B, Tomasi J, Barone V, Curutchet C, Orozco M, Luque F (2009) Acc Chem Res 42:489–492CrossRefGoogle Scholar
  5. 5.
    Cramer C, Truhlar D (2009) Acc Chem Res 42:493–497CrossRefGoogle Scholar
  6. 6.
    Guthrie J (2009) J Phys Chem B 113:4501–4507CrossRefGoogle Scholar
  7. 7.
    Nicholls A, Wlodek S, Grant J (2009) J Phys Chem B 113:4521–4532CrossRefGoogle Scholar
  8. 8.
    Ribeiro RF, Marenich AV, Cramer CJ, Truhlar DG (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9333-9
  9. 9.
    Avdeef A (2007) Adv Drug Deliv Rev 59:568–590CrossRefGoogle Scholar
  10. 10.
    Cesaro A, Russo E, Crescenzi V (1976) J Phys Chem 80:335–339CrossRefGoogle Scholar
  11. 11.
    Hopfinger AJ, Esposito EX, Llinàs A, Glen RC, Goodman JM (2009) J Chem Inf Model 49:1–5CrossRefGoogle Scholar
  12. 12.
    Bardi G, Bencivenni L, Ferro D, Martini B, Cesaro SN, Teghil R (1980) Thermochimica Acta 40:275–282CrossRefGoogle Scholar
  13. 13.
    Kozyro AA, KABO GY, Soldatova TV, Simirskii VV, GOGOLINSKII V, Krasulin AP, Dudarevich NM (1992) Russ J Phys Chem 66:1374–1377Google Scholar
  14. 14.
    De Wit HGM, Van Miltenburg JC, De Kruif CG (1983) J Chem Thermodyn 15:651–663CrossRefGoogle Scholar
  15. 15.
    Reid RC, Prausnitz JM, Poling BE (1987) The properties of gases and liquids. MacGraw-Hill, New York, p 256Google Scholar
  16. 16.
    Emel’yanenko VN, Verevkin SP (2008) J Chem Thermodyn 40:1661–1665CrossRefGoogle Scholar
  17. 17.
    Guthrie JP (1976) Can J Chem 54:202–209CrossRefGoogle Scholar
  18. 18.
    Guthrie JP (1986) Can J Chem 64:635–640CrossRefGoogle Scholar
  19. 19.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery Jr JA, Vreven T, Kudin KN, Burant JC et al (2003) Gaussian 03, Revision B. 04, Gaussian, Inc., PittsburghGoogle Scholar
  20. 20.
    Bergström CAS, Norinder U, Luthman K, Artursson P (2002) Pharm Res 19:182–188CrossRefGoogle Scholar
  21. 21.
    Perlovich G, Kurkov S, Kinchin A, Bauer-Brandl A (2004) AAPS J 6:22–30Google Scholar
  22. 22.
    Szterner P (2008) J Chem Eng Data 53:1738–1744CrossRefGoogle Scholar
  23. 23.
    Szterner P, Kaminski M, Zielenkiewicz A (2002) J Chem Thermodyn 34:1005–1012CrossRefGoogle Scholar
  24. 24.
    Allexander KS, Laprade B, Mauger JW, Paruta AN (1978) J Pharm Sci 67:624–627CrossRefGoogle Scholar
  25. 25.
    Perlovich GL, Rodionov SV, Bauer-Br A (2005) Eur J Pharm Sci 24:25–33CrossRefGoogle Scholar
  26. 26.
    Boller A, Wiedemann HG (1998) J Therm Anal Calorim 53:431–439CrossRefGoogle Scholar
  27. 27.
    Kaminski M, Zielenkiewicz W (1985) Calorim Anal Therm 16:281Google Scholar
  28. 28.
    Belaj F, Tripolt R, Nachbaur E (1990) Monatshefte Für Chemie/Chem Mon 121:99–108CrossRefGoogle Scholar
  29. 29.
    Goldberg RN, Tewari YB (1989) J Phys Chem Ref Data 18:809CrossRefGoogle Scholar
  30. 30.
    Oja V, Suuberg EM (1999) J Chem Eng Data 44:26–29CrossRefGoogle Scholar
  31. 31.
    Perlovich GL, Kurkov SV, Bauer-Brandl A (2006) Eur J Pharm Sci 27:150–157CrossRefGoogle Scholar
  32. 32.
    Perlovich GL, Kurkov SV, Bauer-Brandl A (2003) Eur J Pharm Sci 19:423–432CrossRefGoogle Scholar
  33. 33.
    Avdeef A, Berger CM, Brownell C (2000) Pharm Res 17:85–89CrossRefGoogle Scholar
  34. 34.
    To EC, Davies JV, Tucker M, Westh P, Trandum C, Suh KS, Koga Y (1999) J Solution Chem 28:1137–1157CrossRefGoogle Scholar
  35. 35.
    Ross GR, Heideger WJ (1962) J Chem Eng Data 7:505–507CrossRefGoogle Scholar
  36. 36.
    Cammenga HK, Schulze FW, Theuerl W (1977) J Chem Eng Data 22:131–134CrossRefGoogle Scholar
  37. 37.
    Filosofo I, Merlin M, Rostagni A, Nuovo Cimento II (1943–1954) 7 (1950) 69–75Google Scholar
  38. 38.
    Tang IN, Munkelwitz HR (1991) J Colloid Interf Sci 141:109–118CrossRefGoogle Scholar
  39. 39.
    Miller MM, Ghodbane S, Wasik SP, Tewari YB, Martire DE (1984) J Chem Eng Data 29:184–190CrossRefGoogle Scholar
  40. 40.
    Ruelle P, Kesselring UW (1997) Chemosphere 34:275–298CrossRefGoogle Scholar
  41. 41.
    Shiu WY, Wania F, Hung H, Mackay D (1997) J Chem Eng data (print) 42:293–297CrossRefGoogle Scholar
  42. 42.
    Weil L, Dure G, Quentin KE (1974) Z Wasser-Abwasser-Forsch. 7:169–175Google Scholar
  43. 43.
    Verevkin SP, Emel’yanenko VN, Klamt A (2007) J Chem Eng Data 52:499–510CrossRefGoogle Scholar
  44. 44.
    Farmer WJ, Yang MS, Letey J, Spencer WF (1980) Soil Sci Soc Am J 44:676–680CrossRefGoogle Scholar
  45. 45.
    Sears GW, Hopke ER (1949) J Am Chem Soc 71:1632–1634CrossRefGoogle Scholar
  46. 46.
    Wania F, Shiu WY, Mackay D (1994) J Chem Eng Data 39:572–577CrossRefGoogle Scholar
  47. 47.
    Altschuh J, Br\üggemann R, Santl H, Eichinger G, Piringer OG (1999) Chemosphere 39:1871–1887CrossRefGoogle Scholar
  48. 48.
    Atlas E, Velasco A, Sullivan K, Giam CS (1983) Chemosphere (Oxford) 12:1251–1258Google Scholar
  49. 49.
    Jantunen LM, Bidleman TF (2006) Chemosphere 62:1689–1696CrossRefGoogle Scholar
  50. 50.
    Hellmann H (1987) Fresenius Zeitscrift Fuer Analytische Chemie ZACFAU 328:475–479CrossRefGoogle Scholar
  51. 51.
    Ten Hulscher TE, Van Der Velde LE, Bruggeman WA (1992) Environ Toxicol Chem 11:1595–1603CrossRefGoogle Scholar
  52. 52.
    Ivin KJ, Dainton FS (1947) Trans Faraday Soc 43:32–35CrossRefGoogle Scholar
  53. 53.
    Warneck P (2007) Chemosphere 69:347–361CrossRefGoogle Scholar
  54. 54.
    Ashworth RA, Howe GB, Mullins ME, Rogers TN (1988) J Hazard Mater 18:25–36CrossRefGoogle Scholar
  55. 55.
    Perlovich GL, Kurkov SV, Hansen LK, Bauer-Brandl A (2004) J Pharm Sci 93:654–666CrossRefGoogle Scholar
  56. 56.
    Perlovich GL, Kurkov SV, Kinchin AN, Bauer-Brandl A (2003) J Pharm Sci 92:2502–2511CrossRefGoogle Scholar
  57. 57.
    Perlovich GL, Kurkov SV, Kinchin AN, Bauer-Brandl A (2004) Eur J Pharm Biopharm 57:411–420CrossRefGoogle Scholar
  58. 58.
    Brisset JL (1985) J Chem Eng Data 30:381–383CrossRefGoogle Scholar
  59. 59.
    LePree JM, Mulski MJ, Connors KA (1994) J Chem Soc, Perkin Trans 2:1491–1497Google Scholar
  60. 60.
    Ferro D, Piacente V (1985) Thermochimica Acta 90:387–389CrossRefGoogle Scholar
  61. 61.
    Majury TG (1956) Chem Ind 349–350Google Scholar
  62. 62.
    Malaspina L, Gigli R, Bardi G, Maria GD (1973) J Chem Thermodyn 5:699–706CrossRefGoogle Scholar
  63. 63.
    Sawanoi Y, Shimbo Y, Tabata I, Hisada K, Hori T (2002) Dyes Pigm 52:29–35CrossRefGoogle Scholar
  64. 64.
    Shimizu T, Ohkubo S, Kimura M, Tabata I, Hori T (1987) J Soc Dyers Colour 103:132–137Google Scholar
  65. 65.
    Clever HL (2005) J Phys Chem Ref Data 34:2347–2349CrossRefGoogle Scholar
  66. 66.
    Scharlin P, Battino R (1994) Fluid Phase Equilibria 95:137–147CrossRefGoogle Scholar
  67. 67.
    Kawamoto K, Urano K (1989) Chemosphere (Oxford) 19:1223–1231Google Scholar
  68. 68.
    Lunden H, Chim J (1907) Physique 5:145–185Google Scholar
  69. 69.
    Ribeiro da Silva MA, Santos CP, Monte MJ, Sousa CA (2006) J Therm Anal Calorim 83:533–539CrossRefGoogle Scholar
  70. 70.
    Benoit RL, Choux G (1968) Can J Chem 46:3215–3219CrossRefGoogle Scholar
  71. 71.
    Tommila E, Lindell E, Virtalaine M, Laakso R (1969) Suom Kemistil B 42:95Google Scholar
  72. 72.
    Steele WV, Chirico RD, Knipmeyer SE, Nguyen A (1997) J Chem Eng Data 42:1008–1020CrossRefGoogle Scholar
  73. 73.
    Zielenkiewicz W, Szterner P (2004) J Chem Eng Data 49:1197–1200CrossRefGoogle Scholar
  74. 74.
    Wolfenden R, Williams R (1983) J Am Chem Soc 105:1028–1031CrossRefGoogle Scholar
  75. 75.
    Herskovits TT, Harrington JP (1972) Biochemistry 11:4800–4811CrossRefGoogle Scholar
  76. 76.
    Szegezdi J, Csizmadia F (2007) Tautomer generation. pKa based dominance conditions for generating dominant tautomers. In: American Chemical Society Fall National Meeting, ChemAxon Ltd., BudapestGoogle Scholar
  77. 77.
    Klimovich PV, Mobley DL (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9343-7
  78. 78.
    Klamt A, Diedenhofen M (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9354-4
  79. 79.
    Meunier A, Truchon J-F (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9339-3
  80. 80.
    Purisima EO, Corbeil CR, Sulea T (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9341-9
  81. 81.
    Soteras I, Orozco M, Luque FJ (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9331-y
  82. 82.
    Ellingson BA, Skillman AG, Nicholls A (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9355-3
  83. 83.
    Nicholls A, Wlodek S, Grant JA (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9334-8
  84. 84.
    Kast SM, Heil J, Güssregen S, Schmidt KF (2010) J Comput Aided Mol Des 24. doi: 10.1007/s10822-010-9340-x

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Matthew T. Geballe
    • 1
    Email author
  • A. Geoffrey Skillman
    • 1
  • Anthony Nicholls
    • 1
  • J. Peter Guthrie
    • 2
  • Peter J. Taylor
    • 3
  1. 1.OpenEye Scientific Software, Inc.Santa FeUSA
  2. 2.Department of ChemistryUniversity of Western OntarioLondonCanada
  3. 3.AstraZenica PharmaceuticalsLondonUK

Personalised recommendations