Skip to main content
SpringerLink
Log in

Drude polarizable force field for aliphatic ketones and aldehydes, and their associated acyclic carbohydrates

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

Abstract

The majority of computer simulations exploring biomolecular function employ Class I additive force fields (FF), which do not treat polarization explicitly. Accordingly, much effort has been made into developing models that go beyond the additive approximation. Development and optimization of the Drude polarizable FF has yielded parameters for selected lipids, proteins, DNA and a limited number of carbohydrates. The work presented here details parametrization of aliphatic aldehydes and ketones (viz. acetaldehyde, propionaldehyde, butaryaldehyde, isobutaryaldehyde, acetone, and butanone) as well as their associated acyclic sugars (d-allose and d-psicose). LJ parameters are optimized targeting experimental heats of vaporization and molecular volumes, while the electrostatic parameters are optimized targeting QM water interactions, dipole moments, and molecular polarizabilities. Bonded parameters are targeted to both QM and crystal survey values, with the models for ketones and aldehydes shown to be in good agreement with QM and experimental target data. The reported heats of vaporization and molecular volumes represent a compromise between the studied model compounds. Simulations of the model compounds show an increase in the magnitude and the fluctuations of the dipole moments in moving from gas phase to condensed phases, which is a phenomenon that the additive FF is intrinsically unable to reproduce. The result is a polarizable model for aliphatic ketones and aldehydes including the acyclic sugars d-allose and d-psicose, thereby extending the available biomolecules in the Drude polarizable FF.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Fadda E, Woods RJ (2010) Drug Discov Today 15(15–16):596

    Article  CAS  Google Scholar 

  2. Guvench O, MacKerell AD Jr (2008) Methods Mol Biol 443:63

    Article  CAS  Google Scholar 

  3. MacKerell AD Jr (2004) J Comput Chem 25(13):1584

    Article  CAS  Google Scholar 

  4. Ponder JW, Case DA (2003) Adv Protein Chem 66:27

    Article  CAS  Google Scholar 

  5. Warshel A, Levitt M (1976) J Mol Biol 103:227

    Article  CAS  Google Scholar 

  6. Fox T, Kollman PA (1998) J Phys Chem B 102:8070

    Article  CAS  Google Scholar 

  7. Gough CA, DeBolt SE, Kollman PA (1992) J Comput Chem 13(8):963

    Article  CAS  Google Scholar 

  8. Jorgensen WL (1986) J Phys Chem 90:1276

    Article  CAS  Google Scholar 

  9. Jorgensen WL, Maxwell DS, Tirado-Rives J (1996) J Am Chem Soc 118:11225

    Article  CAS  Google Scholar 

  10. MacKerell AD, Jr., Karplus M (1991) J Phys Chem 95:10559

    Article  CAS  Google Scholar 

  11. Chen IJ, Yin D, MacKerell AD Jr (2002) J Comput Chem 23(2):199

    Article  CAS  Google Scholar 

  12. Kaminski G, Duffy EM, Matsui T, Jorgensen WL (1994) J Phys Chem 98:13077

    Article  CAS  Google Scholar 

  13. Rizzo RC, Jorgensen WL (1999) J Am Chem Soc 121:4827

    Article  CAS  Google Scholar 

  14. Yin D, MacKerell AD Jr (1998) J Comput Chem 19(3):334

    Article  CAS  Google Scholar 

  15. Shirts MR, Pitera JW, Swope WC, Pande VS (2003) J Chem Phys 119(11):5740

    Article  CAS  Google Scholar 

  16. Chowdary J, Harder E, Lopes PEM, Huang L, MacKerell AD Jr, Roux B (2013) J Phys Chem B 117:9142

    Article  CAS  Google Scholar 

  17. He X, Lopes PE, MacKerell AD Jr (2013) Biopolymers 99(10):724

    Article  CAS  Google Scholar 

  18. Jiao D, Golubkov PA, Darden TA, Ren P (2008) Proc Natl Acad Sci U S A 105(17):6290

    Article  CAS  Google Scholar 

  19. Jiao D, Zhang J, Duke RE, Li G, Schnieders MJ, Ren P (2009) J Comput Chem 30(11):1701

    Article  CAS  Google Scholar 

  20. Lopes PE, Huang J, Shim J, Luo Y, Li H, Roux B, MacKerell AD, Jr. (2013) J Chem Theory Comput 9(12):5430

    Article  CAS  Google Scholar 

  21. Ponder JW, Wu C, Ren P, Pande VS, Chodera JD, Schnieders MJ, Haque I, Mobley DL, Lambrecht DS, DiStasio RA Jr, Head-Gordon M, Clark GN, Johnson ME, Head-Gordon T (2010) J Phys Chem B 114(8):2549

    Article  CAS  Google Scholar 

  22. Savelyev A, MacKerell AD Jr (2014) J Comput Chem 10:1652

    Google Scholar 

  23. Shi Y, Zhu CZ, Martin SF, Ren P (2012) J Phys Chem B 116(5):1716

    Article  CAS  Google Scholar 

  24. Zhang J, Yang W, Piquemal JP, Ren P (2012) J Chem Theory Comput 8(4):1314

    Article  CAS  Google Scholar 

  25. Lopes PE, Roux B, MacKerell AD Jr (2009) Theor Chem Acc 124(1–2):11

    Article  CAS  Google Scholar 

  26. Rick SW, Stuart SJ (2002) Rev Comp Chem 18:89

    CAS  Google Scholar 

  27. Bernardo DN, Ding Y, Krogh-Jespersen K, Levy RM (1994) J Phys Chem 98:4180

    Article  CAS  Google Scholar 

  28. Caldwell J, Dang LX, Kollman PA (1990) J Am Chem Soc 112:9144

    Article  CAS  Google Scholar 

  29. Dang LX (1998) J Phys Chem B 102:620

    Article  CAS  Google Scholar 

  30. Sprik M, Klein ML (1988) J Chem Phys 89(12):7556

    Article  CAS  Google Scholar 

  31. Wallqvist A, Berne BJ (1993) J Phys Chem 97:13841

    Article  CAS  Google Scholar 

  32. Asensio JL, Canada FJ, Chen XH, Khan N, Mootoo DR, Jimenez-Barbero J (2000) Chem Eur J 6(6):1035

    Article  CAS  Google Scholar 

  33. Bryce RA, Vincent MA, Malcolm NOJ, Hillier IH, Burton NA (1998) J Chem Phys 109:3077

    Article  CAS  Google Scholar 

  34. Llanta E, Ando K, Rey R (2001) J Phys Chem B 105:7783

    Article  CAS  Google Scholar 

  35. Patel S, Brooks CL 3rd (2003) J Comput Chem 25:1

    Article  CAS  Google Scholar 

  36. Rick SW, Berne BJ (1996) J Am Chem Soc 118:672

    Article  CAS  Google Scholar 

  37. Rick SW, Stuart SJ, Bader JS, Berne BJ (1995) Studies in Physical and Theoretical. Chemistry 83:31

    Google Scholar 

  38. Yoshii N, Miyauchi R, Miura S, Okazaki S (2000) Chem Phys Lett 317:414

    Article  CAS  Google Scholar 

  39. Kunz A-PE, van Gunsteren WF (2009) J Phys Chem A 113:11570

    Article  CAS  Google Scholar 

  40. van Maaren PJ, van der Spoel D (2001) J Phys Chem B 105:2618

    Article  CAS  Google Scholar 

  41. Ren P, Ponder JW (2002) J Comput Chem 23(16):1497

    Article  CAS  Google Scholar 

  42. Shi Y, Xia Z, Zhang J, Best R, Wu C, Ponder JW, Ren P (2013) J Chem Theory Comput 9(9):4046

    Article  CAS  Google Scholar 

  43. Iczkowski RP, Margrave JL (1961) J Am Chem Soc 83(17):3547

    Article  CAS  Google Scholar 

  44. Mulliken RS (1934) J Chem Phys 2:782

    Article  CAS  Google Scholar 

  45. Parr RG, Pearson RG (1983) J Am Chem Soc 105:7512

    Article  CAS  Google Scholar 

  46. Patel S, Brooks CL, III (2004) J Comp Chem 25(1):1

    Article  CAS  Google Scholar 

  47. Patel S, Brooks CL III (2006) Mol Simul 32(3–4):231

    Article  CAS  Google Scholar 

  48. Banks JL, Kaminski GA, Zhou R, Mainz DT, Berne BJ, Friesner RA (1999) J Chem Phys 110:741

    Article  CAS  Google Scholar 

  49. Stern HA, Kaminski GA, Banks JL, Zhou R, Berne BJ, Friesner RA (1999) J Phys Chem B 103:4730

    Article  CAS  Google Scholar 

  50. Stern HA, Rittner F, Berne BJ, Friesner RA (2001) J Chem Phys 115:2237

    Article  CAS  Google Scholar 

  51. Ponomarev SY, Kaminski GA (2011) J Chem Theory Comput 7(5):1415

    Article  CAS  Google Scholar 

  52. Bauer BA, Warren GL, Patel S (2009) J Chem Theory Comput 5(2):359

    Article  CAS  Google Scholar 

  53. Anisimov VM, Lamoureux G, Vorobyov IV, Huang N, Roux B, MacKerell AD, Jr. (2005) J Chem Theory Comput 1(1):153

    Article  CAS  Google Scholar 

  54. Lamoureux G, MacKerell AD Jr, Roux B (2003) J Chem Phys 119(10):5185

    Article  CAS  Google Scholar 

  55. Yu H, Hansson T, Van Gunsteren WF (2003) J Chem Phys 118(1):221

    Article  CAS  Google Scholar 

  56. Lamoureux G, Roux B (2003) J Chem Phys 119(6):3025

    Article  CAS  Google Scholar 

  57. Yu H, Whitfield TW, Harder E, Lamoureux G, Vorobyov I, Anisimov VM, MacKerell AD, Jr., Roux B (2010) J Chem Theory Comput 6(3):774

    Article  CAS  Google Scholar 

  58. Jana M, MacKerell AD, Jr. (2015) J Phys Chem B 119:7846

  59. Patel DS, He X, MacKerell AD Jr (2015) J Phys Chem B 119:637

    Article  CAS  Google Scholar 

  60. Brooks BR, Brooks CL 3rd, MacKerell AD Jr, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M (2009) J Comput Chem 30(10):1545

    Article  CAS  Google Scholar 

  61. Lamoureux G, Roux B (2003) J Chem Phys 119:5185

    Article  CAS  Google Scholar 

  62. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kale L, Schulten K (2005) J Comput Chem 26:1781

    Article  CAS  Google Scholar 

  63. Jiang W, Hardy DJ, Phillips JC, Mackerell AD, Jr., Schulten K, Roux B (2011) J Phys Chem Lett 2(2):87

    Article  CAS  Google Scholar 

  64. van Gunsteren WF, Billeter SR, Eising AA, Hünenberger PH, Krüger P, Mark AE, Scott WRP, Tironi IG (1996) Biomolecular Simulation: The GROMOS96 Manual and User Guide. BIOMOS b.v. Zürich

    Google Scholar 

  65. Lemkul JA, Roux B, van der Spoel D, MacKerell AD, Jr. (2015) J Comp Chem 36:1480

    Article  CAS  Google Scholar 

  66. Lindert S, Bucher D, Eastman P, Pande V, McCammon JA (2013) J Chem Theory Comput 9(11):4684

    Article  CAS  Google Scholar 

  67. Dequidt A, Devémy J, Pádua AAH (2015) J Chem Inf Model 56(1):260

    Article  CAS  Google Scholar 

  68. Plimpton S (1995) J Comp Phys 117:1

    Article  CAS  Google Scholar 

  69. Brooks BR, Brooks CL III, MacKerell AD Jr, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M (2009) J Comput Chem 30(10):1545

    Article  CAS  Google Scholar 

  70. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Vreven Jr T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda K, Kitao O, Nakai H, Klene M, Li TW, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2003) Gaussian 03. Revision B.04, Gaussian, Inc., Pittsburgh, PA

    Google Scholar 

  71. Shao Y, Fusti-Molnar L, Jung Y, Kussmann J, Ochsenfeld C, Brown ST, Gilbert ATB, Slipchenko LV, Levchenko SV, O’Neill DP, Jr. RAD, Lochan RC, Wang T, Beran GJO, Besley NA, Herbert JM, Lin CY, Voorhis TV, Chien SH, Sodt A, Steele RP, Rassolov VA, Maslen PE, Korambath PP, Adamson RD, Austin B, Baker J, Byrd EFC, Dachsel H, Doerksen RJ, Dreuw A, Dunietz BD, Dutoi AD, Furlani TR, Gwaltney SR, Heyden A, Hirata S, Hsu C-P, Kedziora G, Khalliulin RZ, Klunzinger P, Lee AM, Lee MS, Liang W, Lotan I, Nair N, Peters B, Proynov EI, Pieniazek PA, Rhee YM, Ritchie J, Rosta E, Sherrill CD, Simmonett AC, Subotnik JE, III HLW, Zhang W, Bell AT, Chakraborty AK, Chipman DM, Keil FJ, Warshel A, Hehre WJ, III HFS, Kong J, Krylov AI, Gill PMW, Head-Gordon M, Gan Z, Zhao Y, Schultz NE, Truhlar D, Epifanovsky E, Oana M, Q-Chem (2007) Q-Chem 3.1, Q-Chem, Inc., Pittsburgh, PA

    Google Scholar 

  72. Allen FH, Bellard S, Brice MD, Cartwright BA, Doubleday A, Higgs H, Hummelink T, Hummelink-Peters BG, Kennard O, Motherwell WDS, Rodgers JR, Watson DG (1979) Acta Cryst B35:2331

    Article  Google Scholar 

  73. Hatcher E, Guvench O, MacKerell AD, Jr. (2009) J Chem Theory Comput 5(5):1315

    Article  CAS  Google Scholar 

  74. Kuczera K, Wiorkiewicz JK, Karplus M (1993) MOLVIB: Program for the Analysis of Molecular Vibrations: CHARMM. Harvard University, Cambridge

    Google Scholar 

  75. Scott AP, Radom L (1996) J Phys Chem 100:16502

    Article  CAS  Google Scholar 

  76. Vanommeslaeghe K, Yang M, MacKerell AD, Jr. (2015) J Comp Chem 36(14):1083

    Article  CAS  Google Scholar 

  77. Thole BT (1981) Chem Phys 59(3):341

    Article  CAS  Google Scholar 

  78. Huang L, Roux B (2013) J Chem Theory Comput 9(8):3543

    Article  CAS  Google Scholar 

  79. Lin B, Lopes PE, Roux B, MacKerell AD Jr (2013) J Chem Phys 139(8):084509

    Article  CAS  Google Scholar 

  80. Harder E, Anisimov VM, Vorobyov IV, Lopes PEM, Noskov SY, Jr. ADM, Roux B (2006) J Chem Theory Comput 2(6):1587

    Article  CAS  Google Scholar 

  81. Guvench O, MacKerell AD Jr (2008) J Mol Model 14(8):667

    Article  CAS  Google Scholar 

  82. Lamoureux G, Harder E, Vorobyov I, Roux B, MacKerell AD Jr (2006) Chem Phys Lett 418:245

    Article  CAS  Google Scholar 

  83. Morita A, Kato S (1999) J Chem Phys 110(24):11987

    Article  CAS  Google Scholar 

  84. Schropp B, Tavan P (2008) J Phys Chem B 112(19):6233

    Article  CAS  Google Scholar 

  85. Boys SF, Bernardi F (1970) Mol Phys 19:553

    Article  CAS  Google Scholar 

  86. Ransil B (1961) J Chem Phys 34:2109

    Article  CAS  Google Scholar 

  87. Anisimov VM, Vorobyov IV, Roux B, MacKerell AD, Jr. (2007) J Chem Theory Comput 3(6):1927

    Article  CAS  Google Scholar 

  88. Baker CM, Lopes PE, Zhu X, Roux B, MacKerell AD, Jr. (2010) J Chem Theory Comput 6(4):1181

    Article  CAS  Google Scholar 

  89. Harder E, Anisimov VM, Whitfield T, MacKerell AD Jr, Roux B (2008) J Phys Chem B 112(11):3509

    Article  CAS  Google Scholar 

  90. Lopes PE, Lamoureux G, MacKerell AD Jr (2009) J Comput Chem 30(12):1821

    Article  CAS  Google Scholar 

  91. Lopes PE, Lamoureux G, Roux B, MacKerell AD Jr (2007) J Phys Chem B 111(11):2873

    Article  CAS  Google Scholar 

  92. Vorobyov I, Anisimov VM, Greene S, Venable RM, Moser A, Pastor RW, MacKerell AD, Jr. (2007) J Chem Theory Comp 3:1120

    Article  CAS  Google Scholar 

  93. Zhu X, MacKerell AD Jr (2010) J Comput Chem 31(12):2330

    CAS  Google Scholar 

  94. Lagüe P, Pastor RW, Brooks BR (2004) J Phys Chem B 108(1):363

    Article  CAS  Google Scholar 

  95. Lamoureux G, Harder E, Vorobyov IV, Roux B, MacKerell AD Jr (2006) Chem Phys Lett 418:245

    Article  CAS  Google Scholar 

  96. Neumann M, Steinhauser O (1984) Chem Phys Let 106:563

    Article  CAS  Google Scholar 

  97. Kollman PA (1993) Chem Rev 93:2395

    Article  CAS  Google Scholar 

  98. Deng Y, Roux B (2004) J Phys Chem B 108:16567

    Article  CAS  Google Scholar 

  99. Ryckaert J-P, Ciccotti G, Berendsen HJC (1977) J Comput Phys 23:327

    Article  CAS  Google Scholar 

  100. van Gunsteren WF, Karplus M (1980) J Comput Chem 1(3):266

    Article  Google Scholar 

  101. Pulay P, Fogarasi G, Pang F, Boggs JE (1979) J Am Chem Soc 101:2550

    Article  CAS  Google Scholar 

  102. Lemkul JA, Huang J, Roux B, MacKerell AD Jr (2016) Chem Rev 116(9):4983

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Financial support from the NIH to ADM (GM072558) and computational support from the University of Maryland Computer-Aided Drug Design Center, and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation Grant Number OCI-1053575, are acknowledged.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn St., Baltimore, MD, 21201, USA

    Meagan C. Small, Asaminew H. Aytenfisu, Fang-Yu Lin, Xibing He & Alexander D. MacKerell Jr.

Authors
  1. Meagan C. Small
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Asaminew H. Aytenfisu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fang-Yu Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xibing He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexander D. MacKerell Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander D. MacKerell Jr..

Ethics declarations

Conflict of interest

ADM Jr., is co-founder and Chief Scientific Officer of SilcsBio LLC.

Additional information

M. C. Small and A. H. Aytenfisu contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 327 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Small, M.C., Aytenfisu, A.H., Lin, FY. et al. Drude polarizable force field for aliphatic ketones and aldehydes, and their associated acyclic carbohydrates. J Comput Aided Mol Des 31, 349–363 (2017). https://doi.org/10.1007/s10822-017-0010-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10822-017-0010-0

Keywords

Search

Navigation