Theoretical Chemistry Accounts

, Volume 118, Issue 1, pp 219–240 | Cite as

A tunable QM/MM approach to chemical reactivity, structure and physico-chemical properties prediction

  • Piero Altoè
  • Marco Stenta
  • Andrea Bottoni
  • Marco Garavelli
Regular Article

Abstract

In the last decade combined quantum mechanic/ molecular mechanic (QM/MM) methods have been applied to a large variety of chemical problems. This paper describes a new QM/MM implementation that acts as a flexible computational environment. Specifically, geometry optimizations, frequency calculations and molecular dynamics can be performed on the investigated system that can be split up to three different layers corresponding to different levels of accuracy. Here we report, together with a detailed description of the method and its implementation, some test examples on very different chemical problems, which span the wide and diversified area of chemistry (from ground to excited states topics) and show the flexibility, general applicability and accuracy of the presented hybrid approach. Biochemical, photobiological and supra/super-molecular applications are presented for this purpose: (a) the optimized geometry of a rotaxane is compared with its X-ray structure; (b) the computed absorption spectra of the green fluorescent protein and rhodopsin chromophores in different environments (namely solvent and protein) are compared to the corresponding experimental values and the role of the counter ion and ion pairs in tuning the geometrical and optical properties of charged organic chromophores in polar solvents is explored and discussed; (c) problems and open questions related to the model set-up of a protein are investigated in the framework of the TcPRAC-protein racemase; (d) similarities and differences between the QM and QM/MM reaction path for the HIV1-protease enzymatic mechanism are shown and discussed; (e) the delicate anomeric equilibrium of α- and β − D-glucopyranose in water is investigated via QM/MM optimizations and molecular dynamics to show the reliability of the actual implementation in the simulation of solvation effects and delicate balances. Finally, it will be shown that the current implementation (called COBRAMM: Computations at Bologna Relating Ab-initio and Molecular Mechanics Methods) is more than a simple QM/MM method, but a more general hybrid approach with a modular structure that is able to integrate some specialized programs, which may increase the flexibility/efficiency of QM, MM and QM/MM calculations.

Keywords

QM/MM Reaction mechanisms Solvation Spectroscopy Super/supra-molecules Enzymatic processes 

References

  1. 1.
    Leach AR (2001) Molecular modelling: principles and applications. Pearson Education EMA, UK, pp 1–744Google Scholar
  2. 2.
    Jensen F (1999) Introduction to computational chemistry. Wiley, UK, pp 1–429Google Scholar
  3. 3.
    Bakowies D, Thiel W (1996). J Phys Chem 100:10580–10594CrossRefGoogle Scholar
  4. 4.
    Sherwood P (2000). NIC series 3:285–305Google Scholar
  5. 5.
    Warshel A, Levitt M (1976). J Mol Biol 103:227–249CrossRefGoogle Scholar
  6. 6.
    Gao J (1995) KB Lipkowitz, DB Boyd (eds) In: Reviews in computational chemistry, VHC Publishers New York, pp 119–185Google Scholar
  7. 7.
    Lin H, Truhlar DG (2006). Theor Chem Acc 117:185–199CrossRefGoogle Scholar
  8. 8.
    Gao J, Truhlar DG (2002). Annu Rev Phys Chem 53:467–505CrossRefGoogle Scholar
  9. 9.
    Vreven T, Mennucci B, da Silva CO, Morokuma K, Tomasi J (2001). J Chem Phys 115:62–72CrossRefGoogle Scholar
  10. 10.
    Svensson M, Humbel S, Froese RDJ, Matsubara T, Sieber S, Morokuma K (1996). J Phys Chem 100:19357–19363CrossRefGoogle Scholar
  11. 11.
    Maseras F, Morokuma K (1995). J Comput Chem 16:1170–1179CrossRefGoogle Scholar
  12. 12.
    Sherwood P, de Vries AH, Guest MF, Schreckenbach G, Catlow CRA, et al (2003). J Mol Struct 632:1–28Google Scholar
  13. 13.
    Peng C, Ayala PYS, H. Bernhard, Frisch MJ (1996). J Comput Chem 17:49–56CrossRefGoogle Scholar
  14. 14.
    Vreven T, Morokuma K, Farkas Ö, Schlegel HB, Frisch MJ (2003). J Comput Chem 24:760–769CrossRefGoogle Scholar
  15. 15.
    Klahn M, Braun-Sand S, Rosta E, Warshel A (2005). J Phys Chem B 109:15645–15650CrossRefGoogle Scholar
  16. 16.
    Field MJ, Bash PA, Karplus M (1990). J Comput Chem 11:700–733CrossRefGoogle Scholar
  17. 17.
    Singh UC, Kollman PA (1986). J Comput Chem 7:718–730CrossRefGoogle Scholar
  18. 18.
    Ferre N, Olivucci M (2003). J Mol Struct 632:71–82CrossRefGoogle Scholar
  19. 19.
    Pu J, Gao J, Truhlar DG (2004). J Phys Chem A 108:632–650CrossRefGoogle Scholar
  20. 20.
    Gao J, Amara P, Alhambra C, Field MJ (1998). J Phys Chem A 102:4714–4721CrossRefGoogle Scholar
  21. 21.
    Théry V, Rinaldi D, Rivail J-L, Maigret B, Ferenczy GG (1994). J Comput Chem 15:269–282CrossRefGoogle Scholar
  22. 22.
    Breneman CM, Wiberg KB (1990). J Comput Chem 11:361–373CrossRefGoogle Scholar
  23. 23.
    Singh UC, Kollman PA (1984). J Comput Chem 5:129–145CrossRefGoogle Scholar
  24. 24.
    Besler BH, Jr MKM, Kollman PA (1990). J Comput Chem 11: 431–439CrossRefGoogle Scholar
  25. 25.
    Karlstrom G, Lindh R, Malmqvist P-A, Roos BO, Ryde U, et al (2003). Comput Mater Sci 28:222–239CrossRefGoogle Scholar
  26. 26.
    Frisch MJ 2004 Gaussian 03, Revision C.02; Gaussian, Inc., Wallingford CT, 2004.Google Scholar
  27. 27.
    Ahlrichs R, Bar M, Haser M, Horn H, Kolmel C (1989). Chem Phys Lett 162:165–169CrossRefGoogle Scholar
  28. 28.
    Neese F. 2006. ORCA An ab initio, DFT and semiempirical SCF-MO package.Google Scholar
  29. 29.
    Sinnecker S, Neese F (2006). J Comput Chem 27:1463–1475CrossRefGoogle Scholar
  30. 30.
    Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, et al (2005). J Comput Chem 26:1668–1688CrossRefGoogle Scholar
  31. 31.
    Dudek MJ, Ponder JW (1995). J Comput Chem 16:791–816CrossRefGoogle Scholar
  32. 32.
    Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, et al (2003). J Comput Chem 24:1999–2012CrossRefGoogle Scholar
  33. 33.
    Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004). J Comput Chem 25:1157–1174CrossRefGoogle Scholar
  34. 34.
    Gatti FG, Leon S, Wong JKY, Bottari G, Altieri A, et al (2003). Proc Natl Acad Sci USA 100:10–14CrossRefGoogle Scholar
  35. 35.
    Allinger NL, Yuh YH, Lii JH (1989). J Am Chem Soc 111: 8551–8556CrossRefGoogle Scholar
  36. 36.
    Cossi M, Barone V (1998). J Chem Phys 109:6246–6254CrossRefGoogle Scholar
  37. 37.
    Hawkins GD, Cramer CJ, Truhlar DG (1996). J Phys Chem 100:19824–19839CrossRefGoogle Scholar
  38. 38.
    Corchado JC, Sanchez ML, Aguilar MA (2004). J Am Chem Soc 126:7311–7319CrossRefGoogle Scholar
  39. 39.
    Miura N, Taniguchi T, Monde K, Nishimura S-I (2006). Chem Phys Lett 419:326–332CrossRefGoogle Scholar
  40. 40.
    Momany FA, Appell M, Willett JL, Bosma WB (2005). Carbohydr Res 340:1638–1655CrossRefGoogle Scholar
  41. 41.
    Momany FA, Appell M, Willett JL, Schnupf U, Bosma WB (2006). Carbohydr Res 341:525–537CrossRefGoogle Scholar
  42. 42.
    Geerlings P, De Proft F, Langenaeker W (2003). Chemical Reviews 103:1793–1873CrossRefGoogle Scholar
  43. 43.
    Becke AD (1993). J Chem Phys 98:1372–1377CrossRefGoogle Scholar
  44. 44.
    Cossi M, Rega N, Scalmani G, Barone V (2003). J Comput Chem 24:669–681CrossRefGoogle Scholar
  45. 45.
    Woods RJ, Dwek RA, Edge C, Fraser-Reid JB (1995). J Phys Chem 99:3832–3846CrossRefGoogle Scholar
  46. 46.
    He X, Bell AF, Tonge PJ (2002). J Phys Chem B 106:6056–6066CrossRefGoogle Scholar
  47. 47.
    Nielsen SB, Lapierre A, Andersen JU, Pedersen UV, Tomita S, Andersen LH (2001). Phys Rev Lett 87:228102CrossRefGoogle Scholar
  48. 48.
    Tsien RY (1998). Annu Rev Biochem 67:509–544CrossRefGoogle Scholar
  49. 49.
    Andersen LH, Nielsen IB, Kristensen MB, ElGhazaly MOA, Haacke S, et al (2005). J Am Chem Soc 127:12347–12350CrossRefGoogle Scholar
  50. 50.
    Freedman KA, Becker RS (1986). J Am Chem Soc 108:1245– 1251CrossRefGoogle Scholar
  51. 51.
    Sinicropi A, Andruniow T, Ferre N, Basosi R, Olivucci M (2005). J Am Chem Soc 127:11534–11535CrossRefGoogle Scholar
  52. 52.
    Altoe P, Bernardi F, Garavelli M, Orlandi G, Negri F (2005). J Am Chem Soc 127:3952–3963CrossRefGoogle Scholar
  53. 53.
    Jakalian A, Bush BL, Jack DB, Bayly CI (2000). J Comput Chem 21:132–146CrossRefGoogle Scholar
  54. 54.
    Jakalian A, Jack DB, Bayly CI (2002). J Comput Chem 23: 1623–1641CrossRefGoogle Scholar
  55. 55.
    Martin ME, Negri F, Olivucci M (2004). J Am Chem Soc 126: 5452–5464CrossRefGoogle Scholar
  56. 56.
    Feese MD, Faber HR, Bystrom CE, Pettigrew DW, Remington SJ (1998). Structure 6:1407–1418CrossRefGoogle Scholar
  57. 57.
    Gordon JC, Myers JB, Folta T, Shoja V, Heath LS, Onufriev A (2005). Nucleic Acids Res 33:368–371CrossRefGoogle Scholar
  58. 58.
    Creemers TMH, Lock AJ, Subramaniam V, Jovin TM, Volker S (1999). Nat Struct Mol Biol 6:557–560CrossRefGoogle Scholar
  59. 59.
    Cembran A, Bernardi F, Olivucci M, Garavelli M (2004). J Am Chem Soc 126:16018–16037CrossRefGoogle Scholar
  60. 60.
    Vreven T, Bernardi F, Garavelli M, Olivucci M, Robb MA, Schlegel HB (1997). J Am Chem Soc 119:12687–12688CrossRefGoogle Scholar
  61. 61.
    Cembran A, Gonzalez-Luque R, Altoe P, Merchan M, Bernardi F, et al (2005). J Phys Chem A 109:6597–6605CrossRefGoogle Scholar
  62. 62.
    Andruniow T, Ferre N, Olivucci M (2004). Proc Natl Acad Sci USA 101:17908–17913CrossRefGoogle Scholar
  63. 63.
    Cembran A, Bernardi F, Olivucci M, Garavelli M (2005). Proc Natl Acad Sci USA 102:6255–6260CrossRefGoogle Scholar
  64. 64.
    Houjou H, Inoue Y, Sakurai M (1998). J Am Chem Soc 120:4459–4470CrossRefGoogle Scholar
  65. 65.
    Houjou H, Sakurai M, Inoue Y (1996). Chem Lett 1075–1076Google Scholar
  66. 66.
    Prabu-Jeyabalan M, Nalivaika E, Schiffer CA (2000). J Mol Biol 301:1207–1220CrossRefGoogle Scholar
  67. 67.
    Davies DR (1990). Annu Rev Biophys Biophys Chem 19:189–215CrossRefGoogle Scholar
  68. 68.
    Dreyer GB, Metcalf BW, Tomaszek TA, Carr TJ, Chandler AC, et al (1989). Proc Natl Acad Sci USA 86:9752–9756CrossRefGoogle Scholar
  69. 69.
    Piana S, Bucher D, Carloni P, Rothlisberger U (2004). J Phys Chem B 108:11139–11149CrossRefGoogle Scholar
  70. 70.
    Larsson PE, Marti S, Moliner V, Andres J (2004). Abstracts Papers Am Chem Soc 228:U291Google Scholar
  71. 71.
    Hensen C, Hermann JC, Nam K, Ma S, Gao J, Holtje HD (2004). J Med Chem 47:6673–6680CrossRefGoogle Scholar
  72. 72.
    Cecconi F, Micheletti C, Carloni P, Maritan A (2001). Proteins: Struct, Funct, Genet 43:365–372CrossRefGoogle Scholar
  73. 73.
    Warshel A (1998). J Biol Chem 273:27035–27038CrossRefGoogle Scholar
  74. 74.
    Liu H, Muller-Plathe F, van Gunsteren WF (1996). J Mol Biol 261:454–469CrossRefGoogle Scholar
  75. 75.
    Lee H, Darden TA, Pedersen LG (1996). J Am Chem Soc 118: 3946–3950CrossRefGoogle Scholar
  76. 76.
    Piana S, Sebastiani D, Carloni P, Parrinello M (2001). J Am Chem Soc 123:8730–8737CrossRefGoogle Scholar
  77. 77.
    Harte WEB, Jr. David L (1993). J Am Chem Soc 115:3883–3886CrossRefGoogle Scholar
  78. 78.
    Rodriguez EJ, Angeles TS, Meek TD (1993). Biochemistry 32:12380–12385CrossRefGoogle Scholar
  79. 79.
    Hyland LJ, Tomaszek TA, Roberts JGD, Carr SA, Magaard VW, et al (1991). Biochemistry 30:8441–8453CrossRefGoogle Scholar
  80. 80.
    Hyland LJ, Tomaszek TA, Meek JTD (1991). Biochemistry 30:8454–8463CrossRefGoogle Scholar
  81. 81.
    Cavalli A, Carloni P, Recanatini M (2006). Chem Rev 106: 3497–3519CrossRefGoogle Scholar
  82. 82.
    Pillai B, K KK, Hosur, VM (2001). Proteins: Struct Funct Genet 43:57–64CrossRefGoogle Scholar
  83. 83.
    Bottoni A, Lanza CZ, Miscione GP, Spinelli D (2004). J Am Chem Soc 126:1542–1550CrossRefGoogle Scholar
  84. 84.
    Bottoni A, Miscione GP, De Vivo M (2005). Proteins: Struct Funct Bioinf 59:118–130CrossRefGoogle Scholar
  85. 85.
    Scott WRP, Schiffer CA (2000). Structure 8:1259–1265CrossRefGoogle Scholar
  86. 86.
    Piana S, Carloni P, Parrinello M (2002). J Mol Biol 319:567–583CrossRefGoogle Scholar
  87. 87.
    Antoniou D, Basner J, Nunez S, Schwartz SD (2006). Chem Rev 106:3170–3187CrossRefGoogle Scholar
  88. 88.
    Warshel A, Sharma PK, Kato M, Xiang Y, Liu H, Olsson MHM (2006). Chem Rev 106:3210–3235CrossRefGoogle Scholar
  89. 89.
    Soriano A, Silla E, Tuñón I, Martí S, Moliner V, Bertrán J (2004). Theor Chem Acc V112:327–334Google Scholar
  90. 90.
    Chamond N, Gregoire C, Coatnoan N, Rougeot C, Freitas LH, et al (2003). J Biol Chem 278:15484–15494CrossRefGoogle Scholar
  91. 91.
    Tonelli RR, Silber AM, Almeida-de-Faria M, Hirata IY, Colli W, Alves MJM (2004). Cell Microbiol 6:733–741CrossRefGoogle Scholar
  92. 92.
    Buschiazzo A, Goytia M, Schaeffer F, Degrave W, Shepard W, et al (2006). Proc Natl Acad Sci USA 103:1705–1710CrossRefGoogle Scholar
  93. 93.
    Schellenberg P, Johnson E, Esposito AP, Reid PJ, Parson WW (2001). J Phys Chem B 105:5316–5322CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Piero Altoè
    • 1
    • 2
  • Marco Stenta
    • 3
  • Andrea Bottoni
    • 1
  • Marco Garavelli
    • 1
  1. 1.Dipartimento di Chimica ‘G. Ciamician’Universita’ di BolognaBolognaItaly
  2. 2.INSTM, UdR BolognaBolognaItaly
  3. 3.Dipartimento di Chimica“A. Mangini”Universita’ di BolognaBolognaItaly

Personalised recommendations